ORIGINAL_ARTICLE
Maternal Voluntary Exercise during Pregnancy Enhances the Spatial Learning Acquisition but not the Retention of Memory in Rat Pups via a TrkB-mediated Mechanism: The Role of Hippocampal BDNF Expression
Objective(s): The effect of maternal voluntary exercise on hippocampal BDNF level in rat offspring was studied. In addition, the possible role of hippocampal BDNF receptors in maternal exercise induced enhancement of learning in the rat pups was investigated. Materials and Methods: Pregnant rats have been randomly assigned to sedentary control or voluntary exercise groups. Each of the exercising pregnant rats was given access to a cage that was equipped with a running wheel until the end of their pregnancy. On post natal day (PND) 36, two groups consisted of 7 male rat pups in each group from sedentary or exercised mothers were sacrificed and the hippocampus was dissected for BDNF proteins level determination. Also, bilateral injection of K252a to the hippocampus was used to block the hippocampal BDNF action on PND59 in the rat pups. Results: Voluntary exercise during pregnancy significantly increased the level of BDNF protein in the hippocampus of the rat pups on PND36 compared to the control group (P=0.048). Inhibiting BDNF action abolished the exercise-induced improvement of learning acquisition in offspring in training trials (P=0.0001). No difference was observed in the platform location latency and the time spent in the target in the probe test between two groups. Conclusion : This study demonstrates that voluntary exercise during pregnancy via a TrkB-mediated mechanism enhances the spatial learning acquisition, however, not the retention of memory in the rat pups.
https://ijbms.mums.ac.ir/article_1663_8bc4186c1bb1a3b900d6b682683b365b.pdf
2013-09-01
955
961
10.22038/ijbms.2013.1663
BDNF
Hippocampus
K252a
Memory
TrkB
Offspring
Voluntary exercise
Maziar M
Akhavan
1
Skin Research Center, Laboratory of Protein and Enzyme, Shahid Beheshti University (M.C), Shohada-e Tajrish Hospital, Shahrdari St, Tehran, Iran,Department of Pharmacology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
AUTHOR
Hossein
Miladi-Gorji
miladi331@yahoo.com
2
Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
LEAD_AUTHOR
Mitra
Emami-Abarghoie
3
Department of Pharmacology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
AUTHOR
Manouchehr
Safari
4
Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
AUTHOR
Bizhan
Sadighi-Moghaddam
5
Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
AUTHOR
Abbas A.
Vafaei
6
Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
AUTHOR
Ali
Rashidy-Pour
7
Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
AUTHOR
1. Coles K, Tomporowski PD. Effects of acute exercise on executive processing, short-term and long-term memory. J Sport Sci 2008; 26: 333 – 344.
1
2. Van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266-270.
2
3. Akhavan MM, Foroutan T, Safari M, Sadighi-Moghaddam B, Emami-Abarghoie M, Rashidy-Pour A. Prenatal exposure to maternal voluntary exercise during pregnancy provides protection against mild chronic postnatal hypoxia in rat offspring. Pak J Pharm Sci 2012; 25: 233-238.
3
4. Akhavan MM, Emami-Abarghoie M, Safari M, Sadighi-Moghaddam B, Vafaei AA, Bandegi, AR, et al. Serotonergic and noradrenergic lesion suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups. Neuroscience 2008; 151: 1173–1183.
4
5. Kim H, Lee SH, Kim SS, Yoo JH, Kim CJ. The influence of maternal treadmill running during pregnancy on short-term memory and hippocampal cell survival in rat pups. Int J Dev Neurosci 2007; 25: 243–249.
5
6. Lee HH, Kim H, Lee JW, Kim YS, Yang HY, Chang HK, et al. Maternal swimming during pregnancy enhances short-term memory and neurogenesis in the hippocampus of rat pups. Brain Dev 2006; 28: 147–154.
6
7. Parnpiansil P, Jutapakdeegul N, Chentanez T, Kotchabhakdi N. Exercise during pregnancy increases hippocampal brain-derived neurotrophic factor mRNA expression and spatial learning in neonatal rat pup. Neurosci Lett 2003; 352: 45–48.
7
8. Bick-Sander A, Steiner B, Wolf SA, Babu H, Kempermann G. Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring. Proc Natl Acad Sci USA 2006; 103: 3852-3857.
8
9. O’Callaghan RM, Ohle R, Kelly AM. The effects of forced exercise on hippocampal plasticity in the rat: A comparison of LTP, spatial- and non-spatial learning. Behav Brain Res 2007; 176:362–366.
9
10. Stranahan AM, Zhou Y, Martin B, Maudsley S. Pharmacomimetics of exercise: Novel approaches for hippocampally-targeted neuroprotective agents. Curr Med Chem 2009; 16: 4668-4678.
10
11. van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci, 2005; 25, 8680–8685.
11
12. Van Praag H. Neurogenesis and exercise: Past and future directions. Neuromolecular Med 2008; 10:128–140.
12
13. Ding Q, Vaynman S, Akhavan MM, Ying Z, Gomez – Pinilla F. Insulin- like growth factor 1 interfaces with brain -derived neurotrophic factor - mediated synaptic plasticity to modulate aspects of exercise - induced cognitive function. Neuroscience 2006; 140: 823–833.
13
14. Neeper SA, Gomez-pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 1996; 726: 49-56.
14
15. Vaynman S,Ying Z, Gomez-Pinilla F. Interplay between BDNF and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience 2003; 122:647–657.
15
16. Kafitz KW, Rose CR, Thoenen H, Konnerth A. Neurotrophin-evoked rapid excitation through TrkB receptors. Nature 1999; 401: 918-921.
16
The Role of Hippocampal BDNF Expression Akhavan et al
17
Iran J Basic Med Sci, Vol. 16, No. 9, Sep 2013
18
17. Akhavan MM, Emami-Abarghoie M, Sadighi-Moghaddam B, Safari M, Yousefi Y, Rashidy-Pour A. Hippocampal angiotensin II receptors play an important role in mediating the effect of voluntary exercise on learning and memory in rat. Brain Res 2008; 1232: 132-138.
19
18. Lom B, Cohen-Cory S. Brain-derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo. J Neurosci 1999; 19: 9928–9938.
20
19. Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 2004; 20: 2580- 2590.
21
20. Miladi-Gorji H, Rashidy-Pour A, Fathollahi Y, Akhavan MM, Semnanian S, Safari M. Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: The role of hippocampal brain-derived neurotrophic factor. Neurobiol learn mem 2011; 96: 479-491.
22
21. Vaynman S, Ying Z, Gَmez-Pinilla F. Exercise induces BDNF and synapsin I to specific hippocampal subfields. J Neurosci Res 2004;76: 356-362.
23
22. Ebrahimi S, Rashidy-Pour A,Vafaei AA, Akhavan MM. Central β-adrenergic receptors play an important role in the enhancing effect of voluntary
24
exercise on learning and memory in rat. Behav Brain Res 2010; 208:189–193.
25
23. Adlard PA, Cotman CW. Voluntary exercise protects against stress - induced decreases in brain - derived neurotrohic factor protein expression. Neuroscience 2004; 124: 985–992.
26
24. Fujioka A, Fujioka T, Ishida Y, Maekawa T, Nakamura S.Differential effects of prenatal stress on the morphological maturation of hippocampal neurons. Neuroscience 2006; 141: 907–915.
27
25. Van den Hove DL, Lauder JM, Steepens A, Prickaerts J, Blanco CE, Steinbusch HW. Prenatal stress in the rat alters 5-HT1A receptor binding in the ventral hippocampus. Brain Res 2006; 1090: 29-34.
28
26. Holmes MM, Galea LA, Mistlberger RE, Kempermann G. Adult hippocampal neurogenesis and voluntary running activity: circadian and dose-dependent effects. J Neurosci Res 2004; 76: 216-22.
29
27. Knüsel B, Hefti F. K-252 compounds: modulators of neurotrophin signal transduction. J Neurochem 1992; 59: 1987-96.
30
28. Skup M, Czarkowska-Bauch J, Dwornik A, Macias M, Sulejczak D, Wiater M. Locomotion induces changes in Trk B receptors in small diameter cells of the spinal cord. Acta Neurobiol Exp (Wars). 2000; 60: 371.
31
ORIGINAL_ARTICLE
Evaluation of Immunological Parameters in Purified Protein Derivative Positive Tuberculin Workers
Objective(s): According to the occupationally risk of infection in staff workers who have direct contact with mycobacterium species, we investigated their immunological parameters and compared with healthy purified protein derivative (PPD) negative volunteers. Materials and Methods : We investigated 20 PPD positive volunteers working at Tuberculin Unit of Razi Vaccine and Serum Research Institute and PPD negative healthy controls with no exposure or history of active tuberculosis. The percentages of circulating lymphocyte subpopulations were detected by flowcytometry. IL-4 and IFN-γ production levels were measured by ELISA in supernatants of PPD-stimulated peripheral blood mononuclear cells (PBMCs) culture. Results : Tuberculin workers showed an increase in IFN-γ level and significant decrease of CD4+ T cells percentage and CD4/CD8 ratio compared to PPD negative normal individuals. However the IL-4 production and percentage of other lymphocyte population has been unchanged. Discussion: These observations suggest that the immunological parameters of tuberculin workers with PPD positive reaction, who are occupationally exposed to mycobacterium antigens, could be changed. Future studies will be directed towards cytokine networking and regulatory lymphocytes, which will help us validate the significant data presented in this study.
https://ijbms.mums.ac.ir/article_1664_e3dc24fd0922d30f3821c798cda30c64.pdf
2013-09-01
962
964
10.22038/ijbms.2013.1664
Cytokine
Immunological responses
Lymphocyte population
PPD positive
Shohreh
Azimi
1
Department of Microbiology, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran
AUTHOR
Majid
Tebianian
mtebianian@yahoo.com
2
Razi Vaccine and Serum Research Institute, Karaj, Iran
LEAD_AUTHOR
Nader
Mosavari
3
Razi Vaccine and Serum Research Institute, Karaj, Iran
AUTHOR
Azar
Sabokbar
4
Department of Microbiology, Faculty of Science, Islamic Azad University, Karaj Branch, Karaj, Iran
AUTHOR
Farhad
Jalali
5
Department of Allergy and Clinical Immunology, Rasoul Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Saba
Arshi
6
Department of Allergy and Clinical Immunology, Rasoul Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Reza
Arefpajouhi
7
Razi Vaccine and Serum Research Institute, Karaj, Iran
AUTHOR
Swaminathan S. Tuberculosis, the only infection disease to be declared a global emergency by the WHO, is a major cause of death in adults and children worldwide. J Pediatr 2000; 67:S1-S2
1
2. Texeria CH, Abramo C, Munk ME. Immunological diagnosis of tuberculosis, problems and strategies for success. J Bras Pneumol 2007; 33:323-334.
2
3. Lange C, Mori T. Advances in the diagnosis of tuberculosis. Respirology 2010; 15:220-240.
3
4. Cho SN. Current issues on molecular and immunological diagnosis of tuberculosis. Yonsei Med J 2007; 48:347-359.
4
5. Smith I. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbial Rev 2003; 16:463-496.
5
6. Dietrich J, Doherty TM. Interaction of
6
Mycobacterium tuberculosis
7
with the host: consequence For Vaccine development. APMIS. 2009;117(5-6):440-57
8
7. Schluger NW, Rom WN. The host immune response to tuberculosis. Am J Respir Crit Care Med 1998; 157:679-691.
9
8. Caccamo N, Guggino G, Meraviglia S, Gelsomino G, Di Carlo P, Titone L,
10
Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection. PLoS One 2009; 4:e 5528.
11
9. Uppal SS, Tewari SC,Verma S, Dhot PS. Comparison of CD4
12
+ and CD8+
13
Lymphocyte counts in HIV-Negative Pulomonary TB patients with those in normal blood donors and the effect of antitubercular treatment: Hospital-Based flow cytometric study. Cytometry Clin Cytometry 2004; 61B:20-26.
14
10. Jashua SM. Wood Worth and Samuel M.Behar
15
؟؟. Mycobacterium tuberculosis specific CD8+ T Cells and Their role in immunity.
16
Crit Rev Immunol 2006; 26:317-352.
17
11. Vilcek J, Kilon A, Henriksen-Destefano D, Zemts, A , Davidson DM, Davidson M,
18
Defective gamma-interferon production in peripheral blood leukocytes of patients with acute tuberculosis. J Clin Immunol 198 6; 6:146-51.
19
12. Sodhi A, Gong J, Silva C, Gian D, Barnes PF. Clinical Correlates of interferon gamma production in patients with tuberculosis. Clin Infect Dis 1997; 25:617-620.
20
13. Raje A. Immunology of tuberculosis. Indian J Med Res 2004; 120:213-232.
21
ORIGINAL_ARTICLE
Sphingomyelin Liposomes Containing Soluble Leishmania major antigens Induced Strong Th2 Immune Response in BALB/c Mice
Objective(s): Soluble Leishmania antigens (SLA) provide suitable protection against leishmaniasis in murine model when delivered by an appropriate delivery system. Liposomes have been shown to be suitable vaccine delivery systems against leishmaniasis, however, the phospholipase-A (PLA) activity of SLA is a drawback to prepare a stable liposomal SLA. One strategy to overcome this problem might be using a lipid which is resistant to PLA activity of SLA such as sphingomyelin (SM). The aim of this study was to evaluate the effect of stable SM liposomes containing SLA on the immune response induced against leishmaniasis in BALB/c mice . Materials and Methods: BALB/c mice were immunized subcutaneously, three times with 2-week intervals, with SLA, SM-liposome-SLA, empty liposome or buffer. As criteria for protection, footpads swelling at the site of challenge and foot parasite loads were assessed. The immune responses were also evaluated by determination of IgG subtypes and the level of IFN-γ and IL-4 in cultured splenocytes. Results: The group of mice receiving SM-liposome-SLA, showed a significant large footpad swelling, higher parasite burden in foot and higher IL-4 level compared to the group immunized with buffer. In terms of IgG and IgG isotypes, there was no significant difference between the mice receiving SM-liposome-SLA and the mice that received buffer. Moreover, the immune response induced by SM-liposome-SLA showed no significant difference compared with the one caused by SLA alone. Conclusion: It is concluded that SM-liposome-SLA is not an appropriate strategy to induce Th1 immune response and protect the mice against Leishmaniasis; however, SM-liposomes could be suitable vaccine delivery systems when a Th2 response is needed.
https://ijbms.mums.ac.ir/article_1665_17a9278f5d2dea04495d6b5f98036dc7.pdf
2013-09-01
965
972
10.22038/ijbms.2013.1665
Leishmaniasis
Liposome
Vaccine
Omid
Chavoshian
1
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
AUTHOR
Nazanin
Biari
2
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
AUTHOR
Ali
Badiee
3
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
AUTHOR
Ali
Khamesipour
4
Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Azam
Abbasi
5
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
AUTHOR
Zahra
Saberi
6
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
AUTHOR
Seyed Amir
Jalali
7
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
AUTHOR
Mahmoud Reza
Jaafari
jafarimr@mums.ac.ir
8
Nanotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
2 Biotechnology Research Center, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
1. Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev 2006; 19:111-126.
1
2. Firooz A, Khamesipour A, Ghoorchi MH, Nassiri-Kashani M, Eskandari SE, Khatami A, et al Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial. Arch Dermatol 2006; 142:1575-1579.
2
3. Firooz A, Khatami A, Dowlati Y. Itraconazole in the treatment of cutaneous leishmaniasis. Int J Dermatol 2006; 45:1446-1447.
3
4. Khamesipour A, Rafati S, Davoudi N, Maboudi F, Modabber F. Leishmaniasis vaccine candidates for development: a global overview. Indian J Med Res 2006; 123:423-438.
4
5. Sharifi I, FeKri AR, Aflatonian MR, Khamesipour A, Nadim A, Mousavi MR, et al Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran. Lancet 1998; 351:1540-1543.
5
6. Momeni AZ, Jalayer T, Emamjomeh M, Khamesipour A, Zicker F, Ghassemi RL, et al. A randomised, double-blind, controlled trial of a killed Leishmania major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran. Vaccine 1999; 17:466-472.
6
7. Khalil EA, El Hassan AM, Zijlstra EE, Mukhtar MM, Ghalib HW, Musa B, et al. Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan. Lancet 2000; 356:1565-1569.
7
8. Noazin S, Khamesipour A, Moulton LH, Tanner M, Nasseri K, Modabber F, et al. Efficacy of killed whole-parasite vaccines in the prevention of leishmaniasis: a meta-analysis. Vaccine 2009; 27:4747-4753.
8
9. Shargh VH, Jaafari MR, Khamesipour A, Jaafari I, Jalali SA, Abbasi A, et al. Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis. Vaccine 2012; 30:3957-3964.
9
10. Sharma SK, Dube A, Nadeem A, Khan S, Saleem I, Garg R, et al. Non PC liposome entrapped promastigote antigens elicit parasite specific CD8+ and CD4+ T-cell immune response and protect hamsters against visceral leishmaniasis. Vaccine 2006; 24:1800-1810.
10
11. Scott P, Pearce E, Natovitz P, Sher A. Vaccination against cutaneous leishmaniasis in a murine model. I. Induction of protective immunity with a soluble extract of promastigotes. J Immunol 1987; 139:221-227.
11
12. Ravindran R, Bhowmick S, Das A, Ali N. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis. BMC Microbiol 2010; 10:181.
12
13. Ravindran R, Maji M, Ali N. Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route. Mol Pharm 2012; 9:59-70.
13
14. Merrill AH Jr, Schmelz EM, Dillehay DL, Spiegel S, Shayman JA, Schroeder JJ, et al. Sphingolipids--the enigmatic lipid class: biochemistry, physiology, and pathophysiology. Toxicol Appl Pharmacol 1997; 142:208-225.
14
15. Semple SC, Leone R, Wang J, Leng EC, Klimuk SK, Eisenhardt ML, et al. Optimization and characterization of a sphingomyelin/cholesterol liposome formulation of vinorelbine with promising antitumor activity. J Pharm Sci 2005; 94:1024-1038.
15
16. Claassen E, Westerhof Y, Versluis B, Kors N, Schellekens M, van Rooijen N. Effects of chronic injection of sphingomyelin-containing liposomes on lymphoid and non-lymphoid cells in the spleen. Transient suppression of marginal zone macrophages. Br J Exp Pathol 1988; 69:865-875.
16
17. Noazin S, Modabber F, Khamesipour A, Smith PG, Moulton LH, Nasseri K, et al. First generation leishmaniasis vaccines: a review of field efficacy trials. Vaccine 2008; 26:6759-6767.
17
18. Schubert R. Liposome preparation by detergent removal. Methods Enzymol 2003; 367:46-70.
18
19. Badiee A, Jaafari MR, Khamesipour A. Leishmania major: immune response in BALB/c mice immunized with stress-inducible protein 1 encapsulated in liposomes. Exp Parasitol 2007; 115:127-134.
19
20. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol 1981; 126:1614-1619.
20
21. Soto M, Ramirez L,, Pineda MA, Gonzalez V, et al. Searching Genes Encoding Leishmania Antigens for Diagnosis and Protection. Scholarly Research Exchange 2009; 2009:1-25, Article ID 173039.
21
22. Handman E. Leishmaniasis: current status of vaccine development. Clin Microbiol Rev 2001; 14:229-243.
22
23. Afrin F, Rajesh R, Anam K, Gopinath M, Pal S, Ali N. Characterization of Leishmania donovani antigens encapsulated in liposomes that induce protective immunity in BALB/c mice. Infect Immun 2002; 70:6697-6706.
23
24. Bhowmick S, Ravindran R, Ali N. Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response. Vaccine 2007; 25:6544-6556.
24
25. Afonso LC, Scharton TM, Vieira LQ, Wysocka M, Trinchieri G, Scott P. The adjuvant effect of interleukin-12 in a vaccine against Leishmania major. Science 1994; 263:235-237.
25
26. Mazumder S, Ravindran R, Banerjee A, Ali N. Non-coding pDNA bearing immunostimulatory sequences co-entrapped with leishmanial antigens in cationic liposomes elicits almost complete protection against experimental visceral leishmaniasis in BALB/c mice. Vaccine 2007; 25:8771-8781.
26
27. Passero LF, Laurenti MD, Tomokane TY, Corbett CE, Toyama MH. The effect of phospholipase A2 from Crotalus durissus collilineatus on Leishmania (Leishmania) amazonensis infection. Parasitol Res 2008; 102:1025-1033.
27
28. Melendez AJ. Sphingosine kinase signalling in immune cells: Potential as novel therapeutic targets. Biochim Biophys Acta 2008; 1784:66-75.
28
29. Kolesnick R. The therapeutic potential of modulating the ceramide/sphingomyelin pathway. J Clin Invest 2002; 110:3-8.
29
30. Ballou LR, Laulederkind SJ, Rosloniec EF, Raghow R. Ceramide signalling and the immune response. Biochim Biophys Acta 1996; 1301:273-287.
30
31. Martinova EA. Influence of sphingolipids on T lymphocyte activation. Biochemistry 1998; 63:102-110.
31
32. Nixon GF. Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br J Pharmacol 2009; 158:982-993
32
ORIGINAL_ARTICLE
siRNA Delivery Improvement by Co-formulation of Different Modified Polymers in Erythroleukemic Cell Line K562
Objective(s): siRNA may be a very promising tool for treatment of various diseases especially in cancer therapy due to high specificity. One of the main hurdles applications of siRNAs in vivo is optimization of the delivery strategy, especially the carrier systems. The aim of this study was to optimize siRNA delivery into suspended erythroleukemic cell line K562. Materials and Methods: We applied polyethyleneimine (PEI) and oligoethyleneimine (OEI) derivatives alone or their co-formulation with different agents such as chloroquine (a drug known to alter lysosomal pH and thus to inhibit lysosomal degradation of macromolecules), DOPE (lipophilic agent), succinic acid (introduction of negatively charged to polymer) and transferrin (the ligand of transferring receptor which is over-expressed in many types of tumors and hematopoietic cells). Results: In this study it was shown that utilizing a combination of 70% OEI-HA10 (ten hexyl acrylate residues per one OEI chain) plus 30% of transferin-PEI with Luc-siRNA was highly effective for transfecting K562 cell. This co-formulation silenced luciferase activity up to 70% after short time without any significant inhibition in the luciferase activity in siCONTROL wells. Conclusion: In conclusion, the combination of modified PEI with transferrin and OEI by hexyl acrylate may increase siRNA delivery and reduce toxicity in hematopoietic suspended cells.
https://ijbms.mums.ac.ir/article_1677_c948c0835ece896e6de7cb46f9b5817c.pdf
2013-09-01
973
978
10.22038/ijbms.2013.1677
OEI PEI siRNA delivery Suspended cells Transferrin
Mazdak
Ganjalikhani hakemi
1
Cellular & Molecular Immunology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Immunology Dept., Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
2
AUTHOR
Maryam
Hashemi
2
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
1. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391:806-811. 2. McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 2002; 3:737-747. 3. Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 2003 ;4:457-467. 4. Hannon GJ. RNA interference. Nature 2002; 418:244-251. 5. Dykxhoorn DM, Lieberman J. Knocking down disease with siRNAs. Cell 2006; 126:231-235. 6. Ichim TE, Li M, Qian H, Popov IA, Rycerz K, Zheng X, et al. RNA interference: a potent tool for gene-specific therapeutics. Am J Transplant 2004; 4:1227-1236. 7. Kim W, Kim S. Efficient siRNA delivery with non-viral polymeric vehicles. Pharm Res 2009; 26:657-666. 8. Philipp A, Zhao X, Tarcha P, Wagner E, Zintchenko A. Hydrophobically modified oligoethylenimines as highly efficient transfection agents for siRNA delivery. Bioconjug Chem 2009 ; 20:2055-2061. 9. Wagner E. Polymers for siRNA delivery: inspired by viruses to be targeted, dynamic, and precise. Acc Chem Res 2012; 45:1005-1013.
1
10. Günther M, Lipka J, Malek A, Gutsch D, Kreyling W, Aigner A. Polyethylenimines for RNAi-mediated gene targeting in vivo and siRNA delivery to the lung. Eur J Pharm Biopharm 2011; 77:438-449. 11. Nimesh S. Polyethylenimine as a promising vector for targeted siRNA delivery. Curr Clin Pharmacol 2012; 7:121-130. 12. Kircheis R, Kichler A, Wallner G, Kursa M, Ogris M, Felzmann T, et al. Coupling of cell-binding ligands to polyethylenimine for targeted gene delivery. Gene Ther 1997; 4:409-418. 13. Meyer M, Philipp A, Oskuee R, Schmidt C, Wagner E. Breathing life into polycations: functionalization with pH-responsive endosomolytic peptides and polyethylene glycol enables siRNA delivery. J Am Chem Soc 2008; 130:3272-3273. 14. Meyer M, Dohmen C, Philipp A, Kiener D, Maiwald G, Scheu C, et al. Synthesis and biological evaluation of a bioresponsive and endosomolytic siRNA-polymer conjugate. Mol Pharm 2009; 6:752-762. 15. Kircheis R, Wightman L, Schreiber A, Robitza B, Rossler V, Kursa M, et al. Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application. Gene Ther 2001; 8:28-40. 16. Tietze N, Pelisek J, Philipp A, Roedl W, Merdan T, Tarcha P, et al. Induction of apoptosis in murine neuroblastoma by systemic delivery of transferrinshielded siRNA polyplexes for downregulation of Ran. Oligonucleotides 2008; 18:161-174.
2
17. Wagner E, Cotten M, Foisner R, Birnstiel ML. Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proc Natl Acad Sci USA 1991; 88:4255-4259. 18. Zintchenko A, Philipp A, Dehshahri A, Wagner E. Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. Bioconjug Chem 2008; 19:1448-1455. 19. Ogris M, Steinlein P, Kursa M, Mechtler K, Kircheis R, Wagner E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther 1998; 5:1425-1433. 20. Zenke M, Steinlein P, Wagner E, Cotten M, Beug H, Birnstiel ML. Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoietic cells. Proc Natl Acad Sci U S A 1990; 87:3655-3659. 21. Frِhlich T, Wagner E. Peptide- and polymerbased delivery of therapeutic RNA. Soft Matter 2010; 6:226-234.
3
ORIGINAL_ARTICLE
Effect of Restraint Stress during Gestation on Pentylenetetrazol-Induced Epileptic Behaviors in Rat Offspring
Objective(s):
Epilepsy is a neurodevelopmental disorder which is strongly influenced by genetic and environmental factors. Gestational stress has been shown to be an important factor for affecting seizure susceptibility. The present study was conducted to address whether gestational stress may affect pentylentetrazol (PTZ)-induced epileptic behavior in rat offspring in a sex- and age- dependent manner.
Materials and Methods:
Pregnant rats were divided into control and stressed groups (n=6 in each). In the stressed group, pregnant rats were under restraint stress and held immobile in the Plexiglas tube twice per day one hour per session for three consecutive days started on day 17 of pregnancy. To induce seizure, on postnatal days 15 (P15) and 25 (P25), PTZ (40-50 mg/kg, IP) was injected to rat offspring (n=12, one male and one female from any litter for each group/day). Then, epileptic behaviors of each rat were recorded.
Results:
Epileptic behaviors of stressed pups showed significant changes in comparison to control ones. The time to onset of the first epileptic behavior was shortened while mean duration and frequency of tonic-clonic attacks increased in stressed pups on both P15 and P25. Female offspring were different from male offspring in terms of epileptic behavior. Moreover, focal attacks were more obvious and significantly longer in the offspring of stressed group at the age of 25 days than those of 15 day old.
Conclusion:
Prenatal restraint stress potentiated PTZ-induced epileptic behavior, age and sex dependently, probably due to alteration of neural and endocrine pathways during developmental process. Male and younger rats were more sensitive to stress than female and older ones.
https://ijbms.mums.ac.ir/article_1678_bc90fee2adac0b11dfb1a0d8ea604ec5.pdf
2013-09-01
979
984
10.22038/ijbms.2013.1678
Epileptic behavior
Gestation
Pentylenetetrazol
Rat
Restraint stress
Pariya
Hashemi
1
Department of Physiology, Medical Faculty, Urmia University of Medical Science, Urmia, Iran
AUTHOR
Logman
Ebrahimi
2
Department of Physiology, Medical Faculty, Urmia University of Medical Science, Urmia, Iran
AUTHOR
Ehsan
Saboory
saboory@zums.ac.ir
3
Department of Physiology, Neurophysiology Research Center, Urmia University of Medical Science, Urmia, Iran
AUTHOR
Shiva
Roshan-Milani
shivamilani@umsu.ac.ir
4
Department of Physiology, Neurophysiology Research Center, Urmia University of Medical Science, Urmia, Iran
LEAD_AUTHOR
afterselective reduction of tonic inhibition in GABAA receptor alpha5 subunit-deficient mice. J Neurophysiol 2006; 95:2796-2807.
1
26. Mody IPR. Diversity of inhibitory neurotransmission through GABAA receptors. Trends Neurosci 2004; 27:569-575.
2
27. Szyndler J, Maciejak P, Turzynska D, Sobolewska A, Bidzinski A, Plaznik A. Time course of changes in the concentrations of monoamines in the brain structures of pentylenetetrazole-kindled rats. J Neural Transm 2010; 117:707-718.
3
28. Chadda R, Devaud LL. Sex differences in effects of mild chronic stress on seizure risk and GABAA receptors in rats. Pharmacol Biochem Behav 2004; 78:495-504.
4
29. Inan SY, Aksu F. Influence of sex on the interaction between dizocilpine (MK-801) pretreatment and acute cold-restraint stress in epilepsy susceptibility in an animal study. Gender Med 2008; 5:136-146.
5
30. Peternel S, Pilipovic K, Zupan G. Seizure susceptibility and the brain regional sensitivity to oxidative stress in male and female rats in the lithium-pilocarpine model of temporal lobe epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33:456-462.
6
31. Frye CA. Hormonal influences on seizures: basic neurobiology. Int Rev Neurobiol 2008; 83:27-77.
7
17. Brunson KL, Chen Y, Avishai-Eliner S, Baram TZ. Stress and the developing hippocampus: a double-edged sword? Mol Neurobiol 2003; 27:121-136.
8
18. Lemaire V, Koehl M, Le Moal M, Abrous DN. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci U S A 2000; 97:11032-11037.
9
19. Hosseini-Sharifabad M, Esfandiari E, Hosseini-Sharifabad A. The effect of prenatal exposure to restraint stress on hippocampal granule neurons of adult rat offspring. Iran J Basic Med Sci 2012; 15:1060-1067.
10
20. Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ. Stressed-out, or in (utero)? Trends Neurosci 2002; 25:518-524.
11
21. Jiong L, Jorn O, Carsten O, Jakob C, Dorthe H, Mogens V. Prenatal stress and risk of febrile seizures in children. J Autism Dev Disord 2009; 39:1047-1052.
12
22. Seckl JR. Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 2004; 151 :U49-62.
13
23. Barrot M, Abrous DN, Marinelli M, Rouge-Pont F, Le Moal M, Piazza PV. Influence of glucocorticoids on dopaminergic transmission in the rat dorsolateral striatum. Eur J Neurosci 2001; 13:812-818.
14
24. Kapoor A, Dunn E, Kostaki A, Andrews MH, Matthews SG. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. J Physiol 2006; 572:31-44.
15
25. Glykys J MI. Hippocampal network hyperactivity after
16
1. Heinrichs SC. Neurobehavioral consequences of stressor exposure in rodent models of epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:808-815.
17
2. Ahmadzadeh R, Saboory E, Roshan-Milani S, Pilehvarian AA. Predator and restraint stress during gestation facilitates pilocarpine-induced seizures in prepubertal rats. Dev Psychobiol 2011; 53:806-812.
18
3. Sadaghiani MM, Saboory E. Prenatal stress potentiates pilocarpine-induced epileptic behaviors in infant rats both time and sex dependently. Epilepsy Behav 2010; 18:166-170.
19
4. Christensen J, Li J, Vestergaard M, Olsen J. Stress and epilepsy: a population-based cohort study of epilepsy in parents who lost a child. Epilepsy Behav 2007; 11:324-328.
20
5. Reddy DS, Rogawski MA. Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility. J Neurosci 2002; 22:3795-3805.
21
6. Hess CP, Barkovich AJ. Seizures: emergency neuroimaging. Neuroimaging Clin N Am 2010; 20:619-637.
22
7. Tolmacheva EA, Oitzl MS, van Luijtelaar G. Stress, glucocorticoids and absences in a genetic epilepsy model. Horm Behav 2012; 61:706-710.
23
8. Edwards HE, Dortok D, Tam J, Won D, Burnham WM. Prenatal stress alters seizure thresholds and the development of kindled seizures in infant and adult rats. Horm Behav 2002; 42:437-447.
24
9. Frye CA, Bayon LE. Prenatal stress reduces the effectiveness of the neurosteroid 3 alpha,5 alpha-THP to block kainic-acid-induced seizures. Dev Psychobiol 1999; 34:227-234.
25
10. Weinstock M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 2008; 32:1073-1086.
26
11. Sarkisian MR. Overview of the current animal Mmdels for human seizure and epileptic disorders. Epilepsy Behav 2001; 2:201-216.
27
12. De Lima TC, Rae GA. Effects of cold-restraint and swim stress on convulsions induced by pentylenetetrazol and electroshock: influence of naloxone pretreatment. Pharmacol Biochem Behav 1991; 40:297-300.
28
13. Meilleur S, Aznavour N, Descarries L, Carmant L, Mamer OA, Psarropoulou C. Pentylenetetrazol-induced seizures in immature rats provoke long-term changes in adult hippocampal cholinergic excitability. Epilepsia 2003; 44:507-517.
29
14. Heshmatian B, Roshan-Milani S, Saboory E. Prenatal acute stress attenuated epileptiform activities in neonate mice. Yakhteh Med J 2010; 12:81-86.
30
15. Itoh K, Watanabe M. Paradoxical facilitation of pentylenetetrazole-induced convulsion susceptibility in mice lacking neuronal nitric oxide synthase. Neuroscience 2009; 159:735-743.
31
16. Rangon CM, Fortes S, Lelievre V, Leroux P, Plaisant F, Joubert C, et al. Chronic mild stress during gestation worsens neonatal brain lesions in mice. J Neurosci 2007; 27:7532-7540
32
ORIGINAL_ARTICLE
Expression of Recombinant Streptokinase from Streptococcus Pyogenes and Its Reaction with Infected Human and Murine Sera
Objective(s): Streptokinase (SKa) is an antigenic protein which is secreted by Streptococcus pyogenes. Streptokinase induces inflammation by complement activation, which may play a role in post infectious diseases. In the present study, recombinant streptokinase from S. pyogenes was produced and showed that recombinant SKa protein was recognized by infected human sera using Western blot analysis. Materials and Methods: In this study, the ska gene from S. pyogenes was amplified and cloned into pET32a which is a prokaryotic expression vector. pET32a-ska was transformed to Escherichia coli BL21 (DE3) pLysS and gene expression was induced by IPTG. Protein production was improved by modification of composition of the bacterial culture media and altering the induction time by IPTG. The expressed protein was purified by affinity chromatography using the Ni-NTA resin. The integrity of the product was confirmed by Westernblot analysis using infected mice. Serum reactivity of five infected individuals was further analyzed against the recombinant SKa protein. Results: Data indicated that recombinant SKa protein from S. pyogenes can be recognized by patient and mice sera. The concentration of the purified recombinant protein was 3.2 mg/L of initial culture. The highest amount of the expressed protein after addition of IPTG was obtained in a bacterial culture without glucose with the culture optical density of 0.8 (OD600 = 0.8). Conclusion : Present data shows, recombinant SKa protein has same epitopes with natural form of this antigen. Recombinant SKa also seemed to be a promising antigen for the serologic diagnosis of S. pyogenes infections.
https://ijbms.mums.ac.ir/article_1679_974238f54454f5e82accce53763208cb.pdf
2013-09-01
985
989
10.22038/ijbms.2013.1679
Anti-Streptokinase
Gene Expression
Recombinant Streptokinase Protein
Streptococcus pyogenes
Neda
Molaee
1
Department of Cellular and Molecular Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
AUTHOR
Hamid
Abtahi
abtahi@arakmu.ac.ir
2
Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
LEAD_AUTHOR
Ghasem
Mosayebi
gmosayebi@yahoo.com
3
Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
AUTHOR
1. Nobbs AH, Lamont RJ, Jenkinson HF. Streptococcus adherence and colonization. Microbiol Mol Biol Rev 2009; 73:407-450. Table of Contents.
1
2. Sun H, Ringdahl U, Homeister JW, Fay WP, Engleberg NC, Yang AY, et al. Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science 2004; 305:1283-1286.
2
3. Lizano S, Johnston KH. Structural diversity of streptokinase and activation of human plasminogen. Infect Immun 2005; 73:4451-4453.
3
4. Nordstrand A, Norgren M, Holm SE. Pathogenic mechanism of acute post-streptococcal glomerulonephritis. Scand J Infect Dis 1999; 31:523-537.
4
5. Huang TT, Malke H, Ferretti JJ. The streptokinase gene of group A streptococci: cloning, expression in Escherichia coli, and sequence analysis. Mol Microbiol 1989; 3:197-205.
5
6. Ball MM, Puig J, Iborra F. Cloning and sequencing of the streptokinase gene from Streptococcus pyogenes (CIP 56.57). DNA Seq 1995; 6:33-36.
6
7. Hahn RG, Knox LM, Forman TA. Evaluation of poststreptococcal illness. Am Fam Physician 2005; 71:1949-1954.
7
8. Guarner J, Sumner J, Paddock CD, Shieh WJ, Greer PW, Reagan S, et al. Diagnosis of invasive group a streptococcal infections by using immunohistochemical and molecular assays. Am J Clin Pathol 2006; 126:148-155
8
9. Kreikemeyer B, McIver KS, Podbielski A. Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen-host interactions. Trends Microbiol 2003; 11:224-232.
9
10. Abtahi H, Salmanian AH, Rafati S, Behzadian Nejad G, Mohammad Hassan Z. High level expression of recombinant ribosomal protein (L7/L12) from Brucella abortus and its reactivity with infected human sera. . Biomed J 2004; 8:13-18.
10
11. Mahmoudi S, Abtahi H, Bahador A, Mosayebi G, Salmanian AH. Production of recombinant streptokinase in Escherichia coli and reactivity with immunized mice. Pak J Biol Sci 2010; 13:380-334.
11
12. Sambrook J, Russel D. Molecular Cloning, a laboratory manual: Spring New York: Harbor Laboratory Press; 2001.
12
13. Bradford MM. A dye binding assay for protein. Biochem 1976; 72:248-54.
13
14. Lemos JA, Lin VK, Nascimento MM, Abranches J, Burne RA. Three gene products govern (p)ppGpp production by Streptococcus mutans. Mol Microbiol 2007; 65:1568-1581.
14
15. Lembke C, Podbielski A, Hidalgo-Grass C, Jonas L, Hanski E, Kreikemeyer B. Characterization of biofilm formation by clinically relevant serotypes of group A streptococci. Appl Environ Microbiol 2006; 72:2864- 2375.
15
16. Kreikemeyer B, Nakata M, Oehmcke S, Gschwendtner C, Normann J, Podbielski A. Streptococcus pyogenes collagen type I-binding Cpa surface protein. Expression profile, binding characteristics, biological functions, and potential clinical impact. J Biol Chem 2005; 280:33228-33339.
16
17. Rosch JW, Hsu FF, Caparon MG. Anionic lipids enriched at the ExPortal of Streptococcus pyogenes. J Bacteriol 2007; 189:801-306.
17
18. Chaudhuri B, Paju S, Haase EM, Vickerman MM, Tanzer JM, Scannapieco FA. Amylase-binding protein B of Streptococcus gordonii is an extracellular dipeptidyl-peptidase. Infect Immun 2008; 76:4530-4537.
18
19. Steer AC, Vidmar S, Ritika R, Kado J, Batzloff M, Jenney AW, et al. Normal ranges of streptococcal antibody titers are similar whether streptococci are endemic to the setting or not. Clin Vaccine Immunol 2009; 16:172-115.
19
20. Noegel AA, Blau-Wasser R, Sultana H, Muller R, Israel L, Schleicher M, et al. The cyclase-associated protein CAP as regulator of cell polarity and cAMP signaling in
20
ORIGINAL_ARTICLE
Genetic Variations of Tumor Necrosis Factor –α-308 and Lymphtoxin-α+252 in Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia Patients
Objective(s):
Non- Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL) are two main hematological malignances which have been driven from lymphoid tissue. Genetic polymorphisms in tumor necrosis factor-α (TNF-α) -308 and lymphotoxin-α (LT-α) +252 may affect their transcription and expression which leads to their high plasma level. The frequency of the TNF-α (-308) and LT-α (+ 252) polymorphisms are different for NHL and ALL cases in various populations with different ethnicity. This research is designed to investigate the prevalence and association of TNF-α (-308) and LT-α (+ 252) polymorphisms from NHL and ALL in Azarian patients and healthy individuals from Northwestern part of Iran.
Materials and Methods:
Seventy subjects with ALL and 68 NHL, along with another 130 healthy subjects as control group took part in this study. Genomic DNA was extracted, then genetic polymorphisms in TNF-α and LT-α genes were analyzed with the PCR-RFLP and NCOI as restriction enzyme. A statistical analysis was performed by chi-square test using SPSS software. A P-value of <0.05 was considered statistically significant.
Results: A statistically significant difference of LT-α polymorphism was in NHL patients and control (P-value= 0.008) but there was not any association of TNF-α polymorphism between NHL patients and control group. A significant association for TNF-a variant was in ALL and control (P-value =0.005), however, there was no relationship about LT variant between ALL and control.
Conclusion:
The results show that there are significant differences between TNF-α (-308) and LT-α (+252) genetic polymorphisms respectively in ALL and NHL patients with control group from Northwestern part of Iran.
https://ijbms.mums.ac.ir/article_1680_757503ed11306d385ca7bea887d70690.pdf
2013-09-01
990
995
10.22038/ijbms.2013.1680
Acute lymphocytic leuke-
mia
LT-α
Non-Hodgkin lymphoma
Polymorphism
TNF-α
Hajar
Nasiri
nasirihajar@yahoo.com
1
School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Safar
Farajnia
farajnia@gmail.com
2
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Azim
Rezamand
3
Childeren Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Ali Akbar
MovassaghPour
4
School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Heydar Ali
Esmaeili
5
School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Amir
Monfaredan
6
Tabriz branch, Islamic Azad University of Medical Science, Tabriz, Iran
AUTHOR
Naser
Mobarra
mobarra@goums.ac.ir
7
Clinical Biochemistry Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
AUTHOR
Nasser
Rahimifar
8
School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Leyla
Sahebi
9
Tuberclosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Majid
Farshdousti Hagh
10
Hematology & Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
LEAD_AUTHOR
1. Skibola CF, Curry JD, Nieters A. Genetic susceptibility to lymphoma. Haematologica 2007; 92: 960-969.
1
2. Ibrahim A, Abdel Rahman H, Khorshied M, Rania S, Nasr N, Khorshid O. Tumor necrosis factor alpha-308 and lymphotoxin alpha+252 genetic polymorphisms and the susceptibility to non-Hodgkin lymphoma in Egypt. Leuk Res 2012; 36:694-698.
2
3. Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translation research. Hematology Am Soc Hematol Educ program 2009
3
4. CHAN JK .The new world health organization and classification of lymphoma: the past and present and the future. Hematol Oncol 2001; 19:129-150.
4
5. Morton LM, Purdue MP, Zheng T, Wang SS, Armstrong B, Zhang Y, Chatterjee N, et al . Risk of non-Hodgkin lymphoma associated with germ line
5
variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development. Cancer of Epidemiol Biomarkers Prev 2009; 18:1259-1270.
6
6. Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, et al. Prenatal origin of acute lymphoblastic leukemia in children. Lancet 1999; 354:1499-1503.
7
7. Sandler DP, Ross JA. Epidemiology of acute leukemia in children and adults. Semin Oncol 1997; 24:3-16.
8
8. Greaves M. Molecular genetics, natural history and the demise of childhood leukemia. Eur J Cancer 1999; 35:173-185.
9
9. Kadar K, Kovacs M, Karadi I, Melegh B, Pocsai Z, Mikala G , et al. Polymorphisms of TNF-alpha and LT-alpha genes in multiple myeloma. Leuk Res 2008; 32:1499-1504.
10
10. Purdue MP, Lan Q, Kricker A, Grulich AE, Vajdic CM, Turner J, Whitby D, et al. Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study. Oxford J 2006; 28:704-712.
11
11. Hajeer AH, Hutchinson IV. TNF-α gene polymorphism: Clinical and biological implications. Microsc Res Tech 2000; 50:216-228.
12
12. Takeuchi S, Takeuchi N, Tsukasaki K, Bartram CR, Zimmermann M, Schrappe M, et al. Genetic polymorphisms in the tumour necrosis factor locus in childhood acute lymphoblastic leukaemia. Br J Hematol 2002; 119:985–957.
13
13. Kidas E, Moricke A, Beier R, Welte K, Schrappe M, Stanulla M, et al. Genetic polymorphisms of the lymphotoxin alpha gene are associated with increased risk for lethal infections during induction therapy for childhood acute leukemia: a case-control study. Int J Hematol 2009; 89: 584-591.
14
14. Warzocha K, Ribeiro P, Bienvenu J, Roy P, Charlot C, Rigal D, et al. Genetic Polymorphisms in the Tumor Necrosis Factor Locus Influence Non-Hodgkin's Lymphoma Outcome. Blood 1998; 91:3574-3581.
15
15. Wang SS, Purdue MP, Cerhan JR, Zheng T, Menashe I, Armstrong B, et al. Common gene variants in the tumor necrosis factor (TNF) and TNF receptor super families and NF-kB transcription factors and non-hodgkin lymphoma risk. PLoS One 2009; 4:e5360.
16
16. Cerhan JR, Wang S, Maurer MJ, Ansell SM, Geyer SM, Cozen W, et al. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. Blood 2007; 109:5439-5446.
17
17. Rothman N, Skibola CF, Wang SS, Morgan G, Lan Q, Smith MT, et al. Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. Lancet Oncol 2006; 7:27-38.
18
18. Jrad BB, Chatti A, Laatiri A, Ben Ahmed S, Romdhane A, Ajimi S, et al. Tumor necrosis factor promoter gene polymorphism associated with increased susceptibility to non-Hodgkin’s lymphomas. Eur J Hematol 2006; 78:117–122.
19
19. Wang SS, Slager SS, Brennan P, Holly EA, De Sanjose S, Bernstein L, et al. Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10211 cases
20
and 11905 controls from the International Lymphoma Epidemiology Consortium (InterLymph). Blood 2007; 109:3479–3488.
21
20. Seidemann K, Zimmermann M, Book M, Meyer U, Burkhardt B, Welte K, et al. Tumor necrosis factor and lymphotoxin alfa genetic polymorphisms and outcome in pediatric patients with non-hodgkin's lymphoma: results from berlin-frankfurt-Munster Trial NHL-BFM 95. J Clin Oncol 2005; 23:8414-8421.
22
21. Zhao HY, Chen XY, Lin XB, Zhong XY, Zhong LY, Jiang WQ, et al. Relationship between tumor necrosis factor genetic polymorphisms and acute lymphocytic leukemia. Ai Zheng 2003; 22:861-866.
23
22. Stanulla M, Schrauder A, Welte K, Schrappe M. Tumor necrosis factor and lymphotoxin-alpha
24
genetic polymorphisms and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study of patients treated with BFM therapy. BMC Blood Disorders 2001; 1
25
23. Skibola CF, Bracci PM, Nieters A, Brooks WA, Sanjos S, Hughes AM, et al. Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the interLymph Consortium. Am J Epidemiol 2009; 171:267-276.
26
24. Cerhan JR, Wen LM, Zachary S, Novak AJ, Cunningham JM, Kay NE, et al. Genetic variation in tumor necrosis factor and the nuclear factor-kB canonical pathway and risk of non-Hodgkin's Lymphoma. Cancer Epidemiol Biomarkers Prev 2008; 17:3161-3169.
27
ORIGINAL_ARTICLE
Effects of Multivitamins and Known Teratogens on Chick Cardiomyocytes Micromass Culture Assay
Objective(s): This study aimed to find out whether the chick cardiomyocyte micromass (MM) system could be employed to predict the teratogenecity of common environmental factors. Different multivitamins and over the counter drugs were used in this study. Materials and Methods: White Leghorn 5-day-old embryo hearts were dissected and trypsinized to produce a cardiomyocyte cell suspension in Dulbecco's Modified Eagle's Medium. The cultures were incubated at 370C in 5% CO2 in air, and observations were made at 24, 48 and 144 hr, for the detection of cell beating. Cellular viability was assessed using the resazurin assay and cell protein content was assessed by the kenacid blue assay. It was observed that while not affecting total cell number folic acid, vitamin C, sodium fluoride and ginseng did not significantly reduced cell activity and beating. However cadmium chloride significantly reduced the beating, cell viability and cell protein content in micromass cultures. Results: The results demonstrate the potential of the chick cardiomyocyte MM culture assay to identify teratogens/embryotoxins that alter morphology and function, which may result in either teratogenic outcome or cytotoxicity. Conclusion: This could form part of a screen for developmental toxicity related to cardiac function
https://ijbms.mums.ac.ir/article_1681_657534f64fca791725890a0047b61a61.pdf
2013-09-01
996
1003
10.22038/ijbms.2013.1681
Chick cardiomyocyte
Environmental teratogens
Micromass culture
Multivitamins
Samreen
Memon
samreen_memon@hotmail.com
1
Department of Anatomy Liaquat University of Medical Sciences, Pakistan
LEAD_AUTHOR
Margaret
Pratten
margaret.pratten@nottingham.ac.uk
2
School of Biomedical Sciences, University of Nottingham, UK
AUTHOR
to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol Appl Pharmacol. 2008;230:352-357.
1
39. Verma RJ, Sherlin DMG. Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats. Human Exp Toxicol. 2001;20:619-623.
2
40. Heindel JJ, Bates HK, Price CJ, Marr MC, Myers CB, Schwetz BA. Developmental Toxicity Evaluation of Sodium Fluoride Administered to Rats and Rabbits in Drinking Water. Toxicol Sci. 1996;30:162-177.
3
41. Fu Y, Ji LL. Chronic ginseng consumption attenuates ageassociated oxidative stress in rats. J Nutr. 2003;133:3603-3609.
4
42. Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutr. 2000; 3:473-485.
5
43. Liu P, Xu Y, Yin H, Wang J, Chen K, Li Y. Developmental toxicity research of ginsenoside Rb1 using a whole mouse embryo culture Model. Birth Defects Res B Dev Reprod Toxicol. 2005;74:207-209.
6
44. Liu P, Xu YJ, Yin HJ, Zhang ZF, Wang J, Chen K, et al. Effects of ginsenoside Rb1 on mouse embryonic development in vitro. Wei Sheng Yan Jiu. 2005;34:175-177.
7
45. Liu P, Yin H, Xu Y, Zhang Z, Chen K, Yong L. Effects of ginsenoside Rg1 on postimplantation rat and mouse embryos cultured in vitro. Toxicol in Vitro 2006;20: 234-238.
8
46. Poindexter BJ, Allison AW, Bick RJ, Dasgupta A. Ginseng: Cardiotonic in adult rat cardiomyocytes, cardiotoxic in neonatal rat cardiomyocytes. Life Sci. 2006;79:2337-2344.
9
1. Bailey J, Knight A, Balcombe J. The future of teratology research is in vitro. Biogenic Amin. 2005;19:97-145.
10
2. Brown NA, Spielmann H, Bechter R, Flint OP, Freeman S, Jelinek RJ, et al. Screening chemicals for reproductive toxicity: the current alternatives. Altern Lab Anim. 1995;23:868-882.
11
3. Bournias-Vardiabasis N, Teplitz RL. Use of Drosophilia embryo cell cultures as an in vitro teratogen assay. Teratog Carcinog Mutagen. 1982;2:333-341.
12
4. Hartung T, Bremer S, Casati S, Coecke S, Corvi R, Fortaner S, et al. ECVAM’s response to the changing political environment for alternatives: consequences of the European union chemicals and cosmetics policies. Altern Lab Anim. 2003;31:473-481.
13
5. Genschow E, Scholz G, Brown N, Piersma A, Brady M, Clemann N, et al. Development of prediction models for three in vivo embryotoxicity tests in an ECVAM validation study. In vitr Mol Toxicol. 2000;13:51-66.
14
6. Genschow E, Spielmann H, Scholz G, Seller A, Brown N, Piersma A, et al. The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. Altern Lab Anim. 2002;30:151-176.
15
7. Brown NA. Selection of test chemicals for the ECVAM international validation on in vitro embryotoxicity tests. Altern Lab Anim. 2002;30:177-198.
16
8. Spielmann H, Genschow E, Scholz G, Brown NA, Piersma AH, Brady M, et al. Preliminary results of the ECVAM validation study on three in vitro embryotoxicity tests. Altern Lab Anim. 2001;29:301-303.
17
9. Flint OP, Orton TC. An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. Toxicol Appl Pharmacol. 1984;76:383-395.
18
10. Parsons JF, Rockley J, Richold M. In vitro micromass teratogen test: Interpretation of results from a blind trial of 25 compounds using three separate criteria. Toxicol in Vitro. 1990;4:609-611.
19
11. Tsuchiya T, Bürgin H, Tsuchiya M, Winternitz P, Kistler A. Embryolethality of new herbicides is not detected by the micromass teratogen tests 1991;65:145-149.
20
12. Wiger R, Strottum A, Brunborg G. Estimating chemical developmental hazard in chicken embryo limb bud micromass system. Pharmacol Toxicol. 1988;62:32-37.
21
13. L'Huillier N, Pratten MK, Clothier RH. The relative embryotoxicity of 1,3-dichloro-2-propanol on
22
primary chick embryonic cells. Toxicol in Vitro. 2002;16:433-42.
23
14. Meyer MP, Swann K, Burnstock G, Clarke JDW. The extracellular ATP receptor, cP2Y1, inhibits cartilage formation in micromass cultures of chick limb mesenchyme. Dev Dyn. 2001;222:494-505.
24
15. Hurst HS, Clothier RH, Pratten M. An evaluation of a novel chick cardiomyocyte micromass culture assay with two teratogens/embryotoxins associated with heart defects. Altern Lab Anim. 2007;35:505-514.
25
16. Ahir B, Pratten MK. Association of anxiolytic drugs diazepam and lorazepam, and the antiepileptic valproate, with heart defects-effects on cardiomyocytes in micromass (MM) and embryonic stem cell culture. Reprod Toxicol. 2011;31:66-74.
26
17. Memon S, Pratten MK. Developmental toxicity of ethanol in chick heart in ovo and in micromass culture can be prevented by addition of vitamin C and folic acid. Reprod Toxicol. 2009;28:262-269.
27
18. Memon S, Pratten MK. Teratogenic effects of diabetic conditions in chick heart in ovo and micromass culture may be prevented by addition of vitamin C and folic acid. Reprod Toxicol. 2013;35:117-124.
28
19. Atterwill CK, Johnston H, Thomas SM. Models for the in vitro assessment of neurotoxicity in the nervous system in relation to xenobiotics and neurotrophic factor-mediated events. Neurotoxicology. 1992;13:39-53.
29
20. Tang LS, Wlodarczyk BJ, Santillano DR, Miranda RC, Finnel RH. Developmental cosequences of abnormal folate transport during murine heart morphogenesis. Birth Defects Res A Clin Mol Teratol. 2004;70:449-458.
30
21. Torrens C, Brawley L, Anthony FW, Dance CS, Dunn R, Jackson AA, et al. Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertention. 2006;47:982-987.
31
22. Jaffe GM. Vitamin C. In: Machlin L, ed Handbook of vitamins. New York: Marcel Dekker Inc; 1984. p. 199-244.
32
23. Gilani SH, Alibhai Y. Teratogenicity of metals to chick embryos. J Toxicol Environ Health. 1990;30:23 - 31.
33
24. Thompson J, Hipwell E, Loo HV, Bannigan J. Effects of cadmium on cell death and cell proliferation in chick embryos. Reprod Toxicol. 2005;20:539-548.
34
25. Verma RJ, Guna Sherlin DM. Sodium fluoride-induced hypoproteinemia and hypoglycemia in parental and F1-generation rats and amelioration by vitamins. Food Cheml Toxicol. 2002;40:1781-1788.
35
26. Gibson PS, Powrie R, Star J. Herbal and alternative medicine use during pregnancy: a cross-sectional survey. Obstet Gynecol. 2001;97:S44-S5.
36
27. Clothier R, Starzec G, Pradel L, Baxter V, Jones M, Cox H, et al. The prediction of human skin responses by using the combined in vitro fluorescence leakage/Alamar blue (resazurin) assay. Altern Lab Anim. 2002;30:493–504.
37
28. Knox P, Uphill PF, Fry JR, Benford J, Balls M. The FRAME multicentre project on in vitro cytotoxicology. Food Chem Toxicol. 1986;24:457-463.
38
29. Brown NA, Spielmann H, Bechter R, Flint OP, Freeman S, Jelinek RJ, et al. Screening chemicals for
39
reproductive toxicity: the current alternatives. Altern Lab Anim. 1995;23:868-882.
40
30. Zhang Z, Xu Y, Li L, Han J, Zheng L, Liu P, et al. Prevention of retinoic acid-induced early craniofacial abnormalities by folinic acid and expression of endothelin-1/dHAND in the branchial arches in mouse. Br J Nutr. 2006;96:418-425.
41
31. Botto LD, Correa A. Decreasing the burden of congenital heart anomalies: an epidemiologic evaluation of risk factors and survival. Progress in Pediatr Cardiol. 2003;18:111-121.
42
32. Huhta JC, Hernandez-Robles JA. Homocysteine, Folate, and Congenital Heart Defects. Fetal & Pediatr Pathol. 2005;24:71-79.
43
33. Botto LD, Mulinare J, Erickson JD. Do mutivitamin or folic acid supplements reduce the risk for congenital heart defects? Am J Medl Genet A. 2003;121A:95-101.
44
34. Chan PK, Cheng SH. Cadmium-induced ectopic apoptosis in zebrafish embryos Arch Toxicol. 2003;77:69-79.
45
35. Yano CL, Marcondes MCCG. Cadmium chloride-induced oxidative stress in skeletal muscle cells in vitro. Free Radicl Bio Med. 2005;39:1378-1384.
46
36. Chow HES, Cheng SH. Cadmium Affects Muscle Type Development and Axon Growth in Zebrafish Embryonic Somitogenesis. Toxicol Sci. 2003;73:149-159.
47
37. Chan PK, Cheng SH. Cadmium-induced ectopic apoptosis in zebrafish embryos. Journal Arch Toxicol 2003;77:69-79.
48
38. Izquierdo-Vega JA, Sánchez-Gutiérrez M, Del Razo LM. Decreased in vitro fertility in male rats exposed
49
to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol Appl Pharmacol. 2008;230:352-357.
50
39. Verma RJ, Sherlin DMG. Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats. Human Exp Toxicol. 2001;20:619-623.
51
40. Heindel JJ, Bates HK, Price CJ, Marr MC, Myers CB, Schwetz BA. Developmental Toxicity Evaluation of Sodium Fluoride Administered to Rats and Rabbits in Drinking Water. Toxicol Sci. 1996;30:162-177.
52
41. Fu Y, Ji LL. Chronic ginseng consumption attenuates ageassociated oxidative stress in rats. J Nutr. 2003;133:3603-3609.
53
42. Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutr. 2000; 3:473-485.
54
43. Liu P, Xu Y, Yin H, Wang J, Chen K, Li Y. Developmental toxicity research of ginsenoside Rb1 using a whole mouse embryo culture Model. Birth Defects Res B Dev Reprod Toxicol. 2005;74:207-209.
55
44. Liu P, Xu YJ, Yin HJ, Zhang ZF, Wang J, Chen K, et al. Effects of ginsenoside Rb1 on mouse embryonic development in vitro. Wei Sheng Yan Jiu. 2005;34:175-177.
56
45. Liu P, Yin H, Xu Y, Zhang Z, Chen K, Yong L. Effects of ginsenoside Rg1 on postimplantation rat and mouse embryos cultured in vitro. Toxicol in Vitro 2006;20: 234-238.
57
46. Poindexter BJ, Allison AW, Bick RJ, Dasgupta A. Ginseng: Cardiotonic in adult rat cardiomyocytes, cardiotoxic in neonatal rat cardiomyocytes. Life Sci. 2006;79:2337-2344.
58
ORIGINAL_ARTICLE
Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats
Objective(s): Cerebral hypoperfusion/ischemia (CHI) is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE) on passive avoidance memory and long-term potentiation (LTP) after permanent bilateral common carotid arteries occlusion (2CCAO) in male adult rats. Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1) Sham+Veh, 2) Isch+Veh, 3) Sham+GSE, 4) Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL) was measured and LTP was recorded from hippocampal dentate gyrus (DG) after high frequency stimulation (HFS) in all rats. Results: We found that memory was significantly impaired in rats after CHI (P<0.001) concomitant with hippocampal LTP inhibition (P<0.05, P1 and LTP48 respectively). GSE treatment significantly improved memory impairment and increased hippocampal LTP in rats with 2CCAO. Conclusion: Our results in present study suggest that GSE exhibits therapeutic potential for short-and long-term memories as well as LTP in DG, which is most likely related at least in part to its antioxidative and free radical scavenging actions.
https://ijbms.mums.ac.ir/article_1682_dcf37eabff569d8e69fdf86392c71bd9.pdf
2013-09-01
1004
1010
10.22038/ijbms.2013.1682
grape seed extract
Hypoperfusion-Ischemia
LTP
Memory
Rat
Alireza
Sarkaki
1
Physiology Research Center and Medicinal Plants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
Maryam
Rafieirad
2
Department of Biology, Sciences Faculty, Islamic Azad University, Izeh Branch, Izeh, Iran
AUTHOR
Seyed Ebrahim
Hossini
3
Department of Biology, Sciences & Researches Branch, Islamic Azad University, Fars, Iran
AUTHOR
Yaghoub
Farbood
4
Department of Physiology and Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
LEAD_AUTHOR
Fereshteh
Motamedi
5
Iranian Neurosciences Research Network and Neurosciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
Seyed Mohammad
Taghi Mansouri
6
Department of Pharmacology and Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
Bahareh
Naghizadeh
7
Department of Pharmacology and Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
1. Aliev G, Smith MA, Obrenovich ME, de la Torre JC, Perry G. Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Azheimer disease. Neurotox Res 2003;5:491-504.
1
2. Ni J, Ohta H, Matsumoto K, Watanabe H. Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res 1994;653:231-236.
2
3. Block F. Global ischemia and behavioural deficits. Prog Neurobiol 1999;58:279-295.
3
4. Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. Role of nitric oxide synthases in Parkinson's disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res 2008;33:2416-26.
4
5. Aviram M, Dornfeld L, Kaplan M, Coleman R, Gaitini D, Nitecki S, et al. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases:
5
studies in atherosclerotic mice and in humans. Drugs Exp Clin Res. 2002;28:49-62.
6
6. Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 2001 ;158:195-198.
7
7. Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr 2000;71:1062-76.
8
8. Harukuni I, Bhardwaj A. Mechanisms of brain injury after global cerebral ischemia. Neurol Clin 2006;24:1-21.
9
9. Cechetti F, Worm PV, Pereira LO, Siqueira IR, C AN. The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate. Braz J Med Biol Res 2010;43:1178-1183.
10
10. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 2007;54:162-180.
11
11. Pfleger CM, Wang J, Friedman L, Vittorino R, Conley LM, Ho L, et al. Grape-seed polyphenolic extract improves the eye phenotype in a Drosophila model of tauopathy. Int J Alzheimers Dis 2010;2010.
12
12. Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG. Cellular protection with proanthocyanidins derived from grape seeds. Ann N Y Acad Sci 2002;957:11.
13
13. Sreemantula S, Nammi S, Kolanukonda R, Koppula S, Boini KM. Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model. BMC Complement Altern Med 2005;5:1.
14
14. Andres-Lacueva C, Shukitt-Hale B, GalliR L, Jauregui O, Lamuela-RaventosR M, Joseph JA. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci. 2005;8:10.
15
15. Shukitt-Hale B, Carey A, Simon L, Mark D, Joseph J. Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 2006;22:8.
16
16. Shinno K, Zhang L, Eubanks JH, Carlen PL, Wallace MC. Transient ischemia induces an early decrease of synaptic transmission in CA1 neurons of rat hippocampus: electrophysiologic study in brain slices. J Cereb Blood Flow Metab 1997;17:955-966.
17
17. Karaaslan O, Ulusoy M, Kankaya Y, Tiftikcioglu Y, Kocer U, Kankaya D, et al. Protective effect of grape seed extract against ischaemia/reperfusion injury in a rat epigastricflap model. J Plast Reconstr Aesthet Surg 2010;63:6.
18
18. Wang Y, Thomas P, Zhong J, Bi F, Kosaraju S, Pollard A, et al. Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer's disease mouse. Neurotox Res 2009;15:12.
19
19. Hwang IK, Yoo KY, Kim DS, Jeong YK, Kim JD, Shin HK, et al. Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia. Life Sci 2004;75:1989-2001.
20
20. Badavi M, Mehrgerdi F, Sarkaki A, Naseri M, Dianat M. Effect of grape seed extract on lead induced hypertension and heart rate in rat. Pak J Biol Sci 2008 ;11:6.
21
21. Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle
22
cerebral artery occlusion in rats. Statistical validation. Stroke. 1995;26:627-34.
23
22. Wallace JE, Krauter EE, Campbell BA. Motor and reflexive behavior in the aging rat. J Gerontol. 1980; 35:364-70.
24
23. Saadipour K, Sarkaki A, Alaei H, Badavi M, Rahim F. Forced exercise improves passive avoidance memory in morphine-exposed rats. Pak J Biol Sci 2009;12:1206-1211.
25
24. Paxinos G, Waston V. The rat brain in stereotaxic coordinates. 6 ed. London: Academic press limited; 2006.
26
25. Gureviciene I, Ikonen S, Gurevicius K, Sarkaki A, van Groen T, Pussinen R, et al. Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice. Neurobiol Dis 2004;15:188-195.
27
26. Dahiya K, Aggarwal K, Seth S, Singh V, Sharma TK. Type 2 diabetes mellitus without vascular complications and ischemia modified albumin. Clin Lab 2010;56:187-190.
28
27. Saulle E, Centonze D, Martin AB, Moratalla R, Bernardi G, Calabresi P. Endogenous dopamine amplifies ischemic long-term potentiation via D1 receptors. Stroke. 2002 ;33:2978-2984.
29
28. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22:391-397.
30
29. Cavaglia M, Dombrowski SM, Drazba J, Vasanji A, Bokesch PM, Janigro D. Regional variation in brain capillary density and vascular response to ischemia. Brain Res 2001;910:81-93.
31
30. Banerjee AK, Mandal A, Chanda D, Chakraborti S. Oxidant, antioxidant and physical exercise. Mol Cell Biochem 2003;253:307-312.
32
31. Squire LR, Zola SM. Ischemic brain damage and memory impairment: a commentary. Hippocampus. 1996;6:546-552.
33
32. Floyd RA. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 1999;222:236-45.
34
33. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000;48:4581-9.
35
34. Davalos A, Shuaib A, Wahlgren NG. Neurotransmitters and pathophysiology of stroke: evidence for the release of
36
glutamate and other transmitters/mediators in animals and humans. J Stroke Cerebrovasc Dis 2000;2-8.
37
35. Chun HS, Kim JM, Choi EH, Chang N. Neuroprotective effects of several korean medicinal plants traditionally used for stroke remedy. J Med Food 2008;11:246-251.
38
36. Colbourne F, Li H, Buchan AM, Clemens JA. Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke 1999;30:662-668.
39
37. Collingridge GL, Kehl SJ, McLennan H. The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol. 1983 Jan;334:19-31.
40
38. Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging. 2002; 23:719-35.
41
39. Gottlieb M, Wang Y, Teichberg VI. Blood-mediated scavenging of cerebrospinal fluid glutamate. J Neurochem. 2003 Oct;87(1):119-26.
42
40. Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds-biochemistry and functionality. J Med Food 2003 Winter;6:291-299.
43
41. Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr. 2003;133:3275S-3284S.
44
42. Scalbert A, Johnson IT, Saltmarsh M. Polyphenols: antioxidants and beyond. Am J Clin Nutr 2005; 81:215S-217S.
45
43. Jamshidzadeh A, Baha-al-dini Baigi B, Aram M. The effects of grape seed and grape pomace extracts onspatial memory impairment induced by hyoscine in mice. J Med Plants Res 2010;4:6.
46
Ahn SH, Kim HJ, Jeong I, Hong YJ, Kim MJ, Rhie DJ, et al. Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons. BMC Neurosci 2011; 12:78-88.
47
45. Charradi K, Elkahoui S, Karkouch I, Limam F, Hassine FB, Aouani E. Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat. Neurochem Res 2012; 37:2004–2013.
48
ORIGINAL_ARTICLE
Association of Urinary Lipocalin-2 with Lupus Nephritis
Objective(s):
Lupus nephritis (LN) is the main cause of mortality and disability in systemic lupus erythematosus (SLE) patients. Therefore, utilizing a reliable and non-invasive method for serial measurements of renal function seems to be necessary. The aim of this study was to evaluate the role of urinary lipocalin-2 as a biomarker of renal involvement in SLE patients.
Materials and Methods:
Fifty two lupus patients in this cross sectional study were divided into two groups: patients with and without nephritis. For each group, urinary lipocalin-2, values were measured and reported according to urinary lipocalin-2/creatinine. Urinary lipocalin-2/creatinine sensitivity and specificity for identifying biopsy-proven nephritis were calculated, and a receiver operating characteristic (ROC) curve was constructed.
Results
: The mean urinary lipocalin-2/creatinine value of patients with biopsy-proven LN was 2.99 ± 4.1 ng/mg, and in non-LN patients was 1.16 ± 1.27 ng/mg. Urinary lipocalin-2/creatinine levels in LN patients were significantly higher than those in non-LN patients (P- Value = 0.03). In LN patients, urinary lipocalin-2/creatinine significantly correlated with proteinuria (r = 0.68; P = 0.0001). Using a cutoff value of 0.896 ng/mg, urinary lipocalin-2/creatinine had a sensitivity of 89.7% and a specificity of 39.1% for identifying SLE patients with biopsy-proven LN. The area under the ROC curve was 0.664 ± 0.076 with a 95% confidence interval of 0.52-0.81 (P=0.04). Analysis of variance showed that urinary lipocalin-2/creatinine is the same in different classes of LN (P-value=0.28).
Conclusion:
An important clinical conclusion is that measurement of urinary Lipocalin-2 may result in earlier diagnosis of LN.
https://ijbms.mums.ac.ir/article_1683_7514ccb4c0b885ac24f21702c66c3103.pdf
2013-09-01
1011
1015
10.22038/ijbms.2013.1683
Lupus
Nephritis
SLE
Urinary Lipocalin- 2
Farzaneh
Sharifipour
1
Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Abbasali
Zeraati
2
Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Maryam
Sahebari
3
Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammadreza
Hatef
4
Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Masih
Naghibi
5
Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Zahra
Rezaieyazdi
6
Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mahmoud
Mahmoudi
7
Immunology Research Center (IRC), Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Amir Abbas
Azarian
8
Vice Chancellor for Research Office, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Zahra
Mirfeizi
mirfeiziz@mums.ac.ir
9
Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Katayoun
Samadi
10
Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
1. Mok CC. Biomarkers for lupus nephritis: a critical appraisal.J Biomed Biotechnol 2010; 638413:11.
1
2. Fiehn C. Early diagnosis and treatment in lupus nephritis: how we can influence the risk for terminal renal failure. J Rheumatol 2006; 33:1464–6416.
2
3. Cross J, Jayne D. Diagnosis and treatment of kidney disease. Best Pract Res Clin Rheumatol 2005; 19:785- 798.
3
4. Liu CC, Manzi S, Ahearn JM. Biomarkers for systemic lupus erythematosus: a review and perspective. Curr Opin Rheumatol 2005;17:543–449.
4
5. Bajaj S, Albert L, Gladman DD, Urowitz MB, Hallett DC, Ritchie S. Serial renal biopsy in systemic lupus erythematosus. J Rheumatol 2000; 27:2822–2826.
5
6. Mishra J, Ma Q, Prada A
6
. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003; 4:2534–2443.
7
7. Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand J Clin Lab Invest Suppl 2008; 241:89-94.
8
8. Siew ED, Ware LB, Gebretsadik T
9
.Urine neutrophil gelatinase-associated lipocalin moderatelypredicts acute kidney injury in critically ill adults. J Am Soc Nephrol 2009; 20:1823-6832.
10
9. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005; 365:1231-1238.
11
10. Pitashny M, Schwartz N, Qing X, aili B, Aranow C, Mackay M, et al. Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum 2007; 56:1894-1903.
12
11. Brunner HI, Mueller M, Rutherford C. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 2006; 54:2577-2584.
13
12. Bolignano D, Coppolino G, Campo S. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with severity of renal disease in proteinuric patients. Nephrol Dial Transplant 2008; 23:414-416.
14
13. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, et al. Endocytic delivery of lipocalinsiderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 2005;115:610-621.
15
14. Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, et al. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 2006; 54:2577-2584.
16
15. Rubinstein T, Pitashny M, Putterman C. The novel role of neutrophil gelatinase-B associated lipocalin (NGAL)/ lipocalin-2 as a biomarker for lupus nephritis. Autoimmun Rev 2008; 7:229-234.
17
16. Koura HM, Galal A, Elshamaa MF, Kandil DM, Eman A. Elghorori, Eman S. Khalifa. Urinary neutrophil gelatinase – associated lipocalin as a marker of disease activity inpatients with lupus nephritis. Int J Acad Res 2011; 3:141-146.
18
17. Suzuki M, Wiers KM, Klein-Gitelman MS. Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatr Nephrol 2008; 23:403-412.
19
ORIGINAL_ARTICLE
Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker
Objective(s): Recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. Therefore, in the present study, a series of 19 compounds of phthalimide pharmacophore possessing a variety of substituents (NO2, NH2 , Me, Cl, COOH, MeO) at 2-, 3-, and 4- position of the N-phenyl ring and N-(3-amino-2-methylphenyl) succinimide, were subjected to docking studies in order to inhibit voltage-gated sodium channels. Materials and Methods : Chemical structures of all compounds were designed using HYPERCHEM program and Conformational studies were performed through semi-empirical molecular orbital calculations method followed by PM3 force field. Total energy gradient calculated as a root mean square (RMS) value, until the RMS gradient was 0.01 kcal mol-1. Among all energy minima conformers, the global minimum of compounds was used in docking calculations. Using a model of the open pore of Na channels, docking study was performed by AUTODOCK4.2 program. Results : Docking studies have revealed that these types of ligands interacted mainly with II-S6 residues of NaV1.2 through making hydrogen bonds and have additional hydrophobic interactions with domain I, II, III and IV in the channel's inner pore. Conclusion : These computational studies have displayed that these compounds are capable of inhibiting Na channel, efficiently.
https://ijbms.mums.ac.ir/article_1684_b80800e88e0b17f9ad1b4d7de97460bd.pdf
2013-09-01
1016
1021
10.22038/ijbms.2013.1684
Anticonvulsant
Docking
Molecular modeling
Na channel
Phthalimide
Maryam
Iman
iman1359@yahoo.com
1
Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
AUTHOR
Atefeh
Saadabadi
2
Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
AUTHOR
Asghar
Davood
adavood2001@yahoo.com
3
Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
LEAD_AUTHOR
1. Stefan H, Feuerstein T. Novel anticonvulsant drugs. Pharmacol Ther 2007; 113:165.
1
2. Donner EJ, Snead OC. New generation anticonvulsants for the treatment of epilepsy in children. Neuro Rx 2006; 3:170.
2
3. Brodie MJ. Antiepileptic drug therapy the story so far. Seizure 2010; 19:650-55.
3
4. Lacoste L, Bartolucci S, Lapointey J. Pentylenetetrazole inhibits glutamate dehydrogenase and aspartate aminotransferase, and stimulates GABA aminotransferase in homogenates from rat cerebral cortex. J Physiol Pharmacol 1988; 66:1135-1138.
4
5. Yuesheng W, Jones PJ, Batts TW, Landry V, Patel MK,Brown ML. Ligand-based design and synthesis of novel sodium channel blockers from a combined phenytoin–lidocainepharmacophore. Bioorg Med Chem 2009; 17:7064-7072.
5
6. Goldin AL. Resurgence of sodium channel research. Annu Rev Physiol 2001; 63:871.
6
7. Catterall WA, Goldin AL, Waxman SG. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 2005; 57:397–409.
7
8. Vamecq J, Bac P, Herrenknecht CHJ, Maurois P, Delcourt P, Stables JP. Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore. J Med Chem 2000; 43:1311-1319.
8
9. Małgorzata W, Katarzyna KK. Synthesis and anticonvulsant evaluation of some N-substituted phthalimides. Acta Pol Pharm Drug Res 2009; 66: 249-257.
9
10. Davood A, Iman M. Docking and QSAR studies of b-phenylethylidenehydrazine
10
derivatives as a Gamma-aminobutyric acid aminotransferase inhibitor. Med Chem Res 2011; 20:955-961.
11
11. Lipkind GM, Fozzard HA. Molecular modeling of local anesthetic drug binding by voltage-gated sodium channels. Mol Pharmacol 2005; 68:1611-1622.
12
12. Morris GM, Goodsell, DS, Pique ME, Lindstrom WL, Huey R, Forli S, et al. AutoDock4 and autoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 2009; 30: 2785-2291.
13
13. Cosconati S, Marinelli L, Lavecchia A, Novellino E. Characterizing The 1,4-dihydropyridines binding interactions in the L-type Ca
14
2+ channel: model construction and docking calculations. J Med Chem 2007; 50:1504-1113.
15
14. Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, et al. Structures of {gamma}-aminobutyric acid (GABA) aminotransferase, a pyridoxal50-phosphate, and [2Fe-2S] cluster-containing enzyme, complexedwith {gamma}-ethynyl-GABA and with the antiepilepsydrug vigabatrin. J Biol Chem 2004; 279:363.
16
15. Davood A, Nematollahi A, Iman M, Shafiee A. Synthesis and docking studies of new 1,4-dihydropyridines containing 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent as novel calcium channel agonist. Arch Pharm Res 2009; 32:481-487.
17
16. O'Reilly AO, Khambay BPS, Williamson MS, Field LM, WAllace BA, Emyr Davies TG. Modelling insecticide-binding sites in the voltage-gated sodium channel. Biochem J 2006; 396:255-263.
18
17. Huey R, Morris GM. Using Autodock 4 with Autodocktools: A Tutorial. The Scripps Research Institute, USA. 2008; 54-56.
19
ORIGINAL_ARTICLE
The Extract of Crocus sativus and Its Constituent Safranal, Affect Serum Levels of Endothelin and Total Protein in Sensitized Guinea Pigs
Objective(s): The effect of the extract of Crocus sativus and its constituent, safranal on inflammatory markers in sensitized guinea pigs was examined. Materials and Methods: Ovalbumin (OA) sensitized guinea pigs were given drinking water alone (group S), or drinking water containing three concentrations of safranal, three concentrations of extract and one concentration of dexamethasone, (n=6, for all groups) and serum levels of endotheline-1 (ET-1) and total protein (TP) were assessed. Results: Serum levels of ET-1 and TP in group S were significantly higher than control group (P Conclusion: A preventive effect of the extract of C. sativus and its constituent safranal on serum inflammatory markers in sensitized guinea pigs was shown.
https://ijbms.mums.ac.ir/article_1685_ae4fd56a01345f39e341f37664d44da1.pdf
2013-09-01
1022
1026
10.22038/ijbms.2013.1685
Asthma
Crocus sativus
Endotheline
Inflammation
Safranal
Sensitization
Zahra
Gholamnezhad
1
Applied Physiology Research Centre, and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Hamed
Koushyar
2
Applied Physiology Research Centre, and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Goltaj
Byrami
3
Applied Physiology Research Centre, and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad Hossein
Boskabady
boskabadymh@mums.ac.ir
4
Applied Physiology Research Centre, and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
1. Tarantilis PA, Tsoupras G, Polissiou M. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J Chromatogr A 1995; 699:107-118.
1
2. Rios JL, Recio MC, Giner RM, Manez S. An update review of saffron and its active constituents. Phytother Res 1996; 10:189-193.
2
3. Parizadeh MR, Ghafoori Gharib F, Abbaspour AR, Tavakol Afshar J, Ghayour – Mobarhan M. Effects of aqueous saffron extract on nitric oxide production by two human carcinoma cell lines: Hepatocellular
3
carcinoma (HepG2) and laryngeal carcinoma (Hep2). Avicenna J Phytomed 2011; 1:43-50.
4
4. Vosooghi S, Mahmoudabady M, Neamati A, Aghababa H. The preventive effects of hydroalcoholic extract of saffron on hematological parameters of experimental asthmatic rats. Avicenna J Phytomed 2013; 3: 279-288.
5
5. Mahmoudabady M, Neamati A, Vosooghi S, Aghababa H. Hydroalcoholic extract of Crocus sativus affects on bronchial inflammatory cells in sensitized rats. Avicenna J Phytomed 2013; Epub ahead of print.
6
6. Bathaie SZ, Miri HR, Mohagheghi MA, Mokhtari-Dizaji M, Shahbazfar AA, Hasanzadeh H. Saffron aqueous extract inhibits the chemically-induced gastric cancer progression in the wistar albino rat. Iran J Basic Med Sci 2013; 16:27-38.
7
7. Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A. Protective effect of safranal, a constituent of Crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran J Basic Med Sci 2013; 16:73-82.
8
8. Tamaddonfard E, Farshid AA, Ahmadian E, Hamidhoseyni A. Crocin enhanced functional recovery after sciatic nerve crush injury in rats. Iran J Basic Med Sci 2013; 16:83-90.
9
9. Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 2013; 16:39-46.
10
10. Mousavi SZ, Bathaie SZ. Historical uses of saffron: Identifying potential new avenues for modern research. Avicenna J Phytomed 2011; 1:57-66.
11
11. Boskabady MH, Aslani MR. Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its possible mechanisms. J Pharm Pharmacol 2006; 58:1385-1390.
12
12. Boskabady MH, Ghasemzadeh Rahbardar M, Nemati H, Esmaeilzadeh M. Inhibitory effect of Crocus sativus (saffron) on histamine (H1) receptors of guinea pig tracheal chains. Pharmazie 2010; 65:300-305.
13
13. Nemati H, Boskabady MH, Ahmadzadef Vostakolaei H. Stimulatory effect of Crocus sativus (saffron) on beta2-adrenoceptors of guinea pig tracheal chains. Phytomedicine 2008; 5:1038-1045.
14
14. Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. The Effect of Crocus sativus Extract on Human Lymphocytes' Cytokines and T Helper 2/T Helper 1 Balance. J Med Food 2011; 14:1538-1545.
15
15. Bayrami G, Boskabady MH. The potential effect of the extract of Crocus sativus and safranal on total and differential white blood cells in blood of ovalbumin-sensitized guinea-pigs. Res Pharm Sci 2012; 7:249-255.
16
16. Boskabady MH, Bayrami G, Tabatabaee A. The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs. Phytomedicine 2012; 19:904-911.
17
17. Busse W, Banks-Schlegel SP, Larsen GL. Childhood-versus adult-onset asthma. Am J Respir Crit Care Med 1995; 151:1635-1639.
18
18. Gawlik R, Jastrzebski D, Ziora D, Jarzab J. Concentration of endothelin in plasma and BAL fluid from asthmatic patients. J Physiol Pharmacol 2006; 57:103-110.
19
19. Boskabady MH, Kiani S, Aslani MR. Tracheal responsiveness to both isoprenaline and beta2-adrenoreceptor blockade by propranolol in cigarette smoke exposed and sensitized guinea pigs. Respirology 2006; 11:572-578.
20
20. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci 2005; 8:394-399.
21
21. Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol 2002; 2:7.
22
22. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia 2006; 77:446-448.
23
23. Gelfand EW. Role of histamine in the pathophysiology of asthma: immunomodulatory and anti-inflammatory activities of H1-receptor antagonists. Am J Med 1 2002; 9A:2S-7S.
24
24. Qureshi S, Memon SA, Laghari AJ, Ghanghro AB. Metabolic total protein investigation in local industry workers exposed to acid anhydrids. Sindh Univ Res J 2009; 41: 63- 66.
25
25. Bayrami G, Boskabady MH, Jalali S, Farkhondeh T. The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized Guinea-pigs. J Ethnopharmacol 2013; 147:530-535.
26