Carvacrol and Zataria multiflora influenced the PPARγ agonist effects on systemic inflammation and oxidative stress induced by inhaled paraquat in rat

Document Type : Original Article

Authors

1 Department of Physiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

2 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): The effects of PPAR-γ agonist alone and in combination with carvacrol and Zataria multiflora on inhaled paraquat (PQ) induced-systemic inflammation and oxidative stress were examined.
Materials and Methods: Control group exposed to normal saline aerosol, one group exposed to 54 mg/m3 PQ aerosol and four groups exposed to PQ aerosol and treated with 5 mg/kg/day pioglitazone, pioglitazone + 200 mg/kg/day Z. multiflora extract, pioglitazone + 20 mg/kg/day carvacrol, and 0.03 mg /kg/day dexamethasone for 16 days after the end of exposure to PQ were studied. Exposure to normal saline or PQ was performed every other days for 30 min (8 times). Different variables were measured after the end of treatment period.
Results: PQ exposure significantly increased serum levels of NO2, MDA and IL-6 but dexreased CAT and IFN-γ levels and IFN-γ/IL-6 ratio compared to control group (PConclusion: The effects of combination therapy of pioglitazone with Z. multiflora or carvacrol on inhaled paraquat (PQ) induced-oxidative stress and systemic inflammation were higher than the effects of pioglitazone alone. These results suggested that the effects of the extract and carvacrol may mediated through PPAR-γ receptors.

Keywords

References

1. Dhananjayan V, Ravichandran B. Occupational health risk of farmers exposed to pesticides in agricultural activities. Curr Opin Environ Sci Health 2018;4:31-37.
2. Hu X, Liang Y, Zhao H, Zhao M. Effects of AT-RvD1 on paraquat-induced acute renal injury in mice. Int Immunopharmacol 2019;67:231-238.
3. Dinis-Oliveira R, Duarte J, Sanchez-Navarro A, Remiao F, Bastos M, Carvalho F. Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol 2008;38:13-71.
4. Buendía JA, Chavarriaga GJR, Zuluaga AF. Burden of paraquat poisoning in the  department of Antioquia, Colombia. BMC Pharmacol Toxicol 2019; 20:11.
5. Asadi R, Afshari R. Ten-year disease burden of acute poisonings in Northeast Iran and estimations for national rates. Hum Exp Toxicol 2016; 35:747-59.
6. Kim Sj, Gil HW, Yang JO, Lee EY, Hong SY. The clinical features of acute kidney injury in patients with acute paraquat intoxication. Nephrol Dial Transplant 2008;24:1226-1232.
7. Yoon SC. Clinical outcome of paraquat poisoning. Korean J Intern Med 2009;24:93-94.
8. Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol 2011;72:745-757.
9. Zhao G, Li S, Hong G, Li M, Wu B, Qiu Q, et al. The effect of resveratrol on paraquat-induced acute lung injury in mice and its mechanism. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2016;28:33-37.
10. Sun L, Yan PB, Zhang Y, Wei LQ, Li GQ. Effect of activated charcoal hemoperfusion on renal function in patients with paraquat poisoning. Exp Ther Med 2018;15:2688-2692.
11. Gawarammana  IB, Buckley NA. Medical management of paraquat ingestion. British J Clin Pharmacol 2011;72:745-757.
12. Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2011;2:236-240.
13. Youssef J, Badr MZ. PPARs: history and advances,  Peroxisome Proliferator-Activated Receptors (PPARs). Springer 2013; 1-6.
14. Wang L, Waltenberger B, Pferschy-Wenzig E-M, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem Pharmacol 2014;92:73-89.
15. Fujiki Y, Okumoto K, Kinoshita N, Ghaedi K. Lessons from peroxisome-deficient Chinese hamster ovary (CHO) cell mutants. Biochim Biophys Acta 2006;1763:1374-1381.
16. Ohtera A, Miyamae Y, Yoshida K, Maejima K, Akita T, Kakizuka A, et al. Identification of a new type of covalent PPARγ agonist using a ligand-linking strategy. ACS Chem Biol 2015;10:2794-2804.
17. Sajed H, Sahebkar A, Iranshahi M. Zataria multiflora Boiss.(Shirazi thyme)—an ancient condiment with modern pharmaceutical uses. J Ethnopharmacol 2013;145:686-698.
18. Khazdair MR, Ghorani V, Alavinezhad A, Boskabady MH. Pharmacological effects of Zataria multiflora Boiss L. and its constituents focus on their anti-inflammatory, anti-oxidant, and immunomodulatory effects. Fundam Clin Pharmacol 2018;32:26-50.
19. Ahmadipour A, Sharififar F, Nakhaipour F, Samanian M, Karami-Mohajeri S. Hepatoprotective effect of Zataria multiflora Boisson cisplatin-induced oxidative stress in male rat. IJMS 2015;8:275.
20. Burleigh-Flayer H, Alarie Y. Concentration-dependent respiratory response of guinea pigs to paraquat aerosol. Arch Toxicol 1987;59:391-396.
21. Malekinejad H, Khoramjouy M, Hobbenaghi R, Amniattalab A. Atorvastatin attenuates the paraquat-induced pulmonary inflammation via PPARγ receptors: A new indication for atorvastatin. Pestic Biochem Phys 2014;114:79-89.
22. Jalali S, Boskabady MH, Rohani AH, Eidi A. The effect of carvacrol on serum cytokines and endothelin levels of ovalbumin sensitized guinea-pigs. Iran J Basic Med Sci  2013;16:615-619.
23. Heydari M, Mokhtari-Zaer A, Amin F, Memarzia A, Saadat S, Hosseini M, et al. The effect of Zataria multiflora hydroalcoholic extract on memory and lung changes induced by rats that inhaled paraquat. Nutr Neurosci 2019:1-14.
24. Alemán-Laporte J, Bandini LA, Garcia-Gomes MS, Zanatto DA, Fantoni DT, Amador Pereira MA, et al. Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization, Laboratory animals. 2019:0023677219850211.
25. Hakimizadeh E, Askary A, Shamsizadeh A, Rahmani M, Vazirinejad R, Ayoobi F, et al. Effect of hydro-alcoholic extract of Artemisia aucheri on castor oil-induced diarrhea in male rat. J Shahrekord Univ Med Sci 2013;15-22.
26. Khazdair MR, Ghorani V, Alavinezhad A, Boskabady MH. Effect of Zataria multiflora on serum cytokine levels and pulmonary function tests in sulfur mustard-induced lung disorders: A randomized double-blind clinical trial. J Ethnopharmacol 2020;248:112325-112333.
27. Shakeri F, Soukhtanloo M, Boskabady MH. The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, anti-oxidant biomarkers in rat model of asthma. Iran J Basic Med Sci 2017;20:155-165.
28. Saadat S, Beheshti F, Askari VR, Hosseini M, Roshan NM, Boskabady MH. Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats. Respir Res 2019;20:96.
29. Facecchia K, Fochesato LA, Ray SD, Stohs SJ, Pandey S. Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies. J Toxicol 2011;2011:683728-683739.
30. Cheresh P, Kim S-J, Tulasiram S, Kamp DW. Oxidative stress and pulmonary fibrosis. Biochim Biophys Acta 2013;1832:1028-1040.
31. Keeling PL, Smith LL. Relevance of NADPH depletion and mixed disulphide formation in rat lung to the mechanism of cell damage following paraquat administration. Biochem Pharmacol 1982;31:3243-3249.
32. Suntres ZE. Exploring the potential benefit of natural product extracts in paraquat toxicity. Fitoterapia 2018; 131: 160-167.
33. Meng Z, Dong Y, Gao H, Yao D, Gong Y, Meng Q, et al. The effects of ω-3 fish oil emulsion-based parenteral nutrition plus combination treatment for acute paraquat poisoning. Glob J Med Res 2019;47:600-614.
34. Kianmehr M, Rezaei A, Hosseini M, Khazdair MR, Rezaee R, Askari VR, et al. Immunomodulatory effect of characterized extract of Zataria multiflora on Th1, Th2 and Th17 in normal and Th2 polarization state. Food Chem Toxicol 2017;99:119-127.
35. Piguet PF, Collart MA, Grau GE, Sappino AP, Vassalli P. Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. Nature 1990;344:245.
36. Zou C, Hu H, Xi X, Shi Z, Wang G, Huang X. Pioglitazone protects against renal ischemia-reperfusion injury by enhancing anti-oxidant capacity. J Surg Res 2013;184:1092-1095.
37.  Al Rouq F, El Eter E. PPAR-γ activator induces neuroprotection in hypercholesterolemic rats subjected to global cerebral ischemia/reperfusion injury: In vivo and in vitro inhibition of oxidative stress. Exp Gerontol 2014;51:1-7.
38. Storer PD, Xu J, Chavis J, Drew PD. Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: implications for multiple sclerosis. J Neuroimmunol 2005;161:113-122.
39. McKinnon B, Bersinger NA, Mueller MD. Peroxisome proliferating activating receptor gamma–independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones. Fertil Steril 2012;97:657-664.
40. Khazdair M, Alavinezhad A, Boskabady M. Carvacrol ameliorates haematological parameters, oxidant/anti-oxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: A randomized double-blind clinical trial. J Clin Pharm Ther 2018;43:664-674.
41. Khazdair MH, Rajabi O, Balali-Moodd M, Beheshtie F, Boskabady MH. The effect of Zataria multiflora on pulmonary function tests, hematological and oxidant/anti-oxidant parameters in sulfur mustard exposed veterans, a randomized doubled-blind clinical trial. Environ Toxicol Pharmacol 2018;58:180-188.
42. Khazdair MR, Boskabady MH. The effect of carvacrol on inflammatory mediators and respiratory symptoms in veterans exposed to sulfur mustard, a randomized, placebocontrolled trial. Respir Med 2019;150:21-29.
43. Kianmehr M, Rezaei A, Boskabady MH. Effect of carvacrol on various cytokines genes expression in splenocytes of asthmatic mice. Iran J Basic Med Sci 2016; 19: 402-410.
44. Boskabady MH, Mehrjardi SS, Rezaee A, Rafatpanah H, Jalali S. The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance. J Ethnopharmacol 2013; 150: 1024-1031.
45. Hotta M1, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue H. Carvacrol, a component of thyme oil, activates PPARalpha and gamma and suppresses COX-2 expression. J Lipid Res 2010;51:132-139.
Iranian Journal of Basic Medical Sciences
Volume 23, Issue 7
July 2020
Pages 930-936

Files

Share

How to cite

Statistics