Aortic Ischemia-Reperfusion Injury and Potency of Fluoxetine

Document Type : Original Article

Authors

1 Istanbul University-Cerrahpaşa, Cerrahpasa Medical Faculty, Department of Physiology, Istanbul, Turkey

2 Vocational Sch. of Health Sciences, Istanbul University-Cerrahpaşa, Istanbul, Turkey

3 Istanbul Aydın University, Medical Faculty, Department of Histology & Embryology, Istanbul, Turkey

4 Department of Physiology, Medical Faculty, Bezmialem University, Istanbul, Turkey

5 Istanbul University, Istanbul Faculty of Medicine, Department of Histology & Embryology, Istanbul, Turkey

6 Istanbul Aydın University, Medical Faculty, Department of Obstetrics & Gynecology, Istanbul, Turkey

7 Tekirdağ Namık Kemal University, Medical Faculty, Department of Physiology, Tekirdağ, Turkey

8 Istanbul Aydın University, Medical Faculty, Department of Physiology, Istanbul, Turkey

Abstract

OBJECTIVE(S): Due to cross-clamping of the aorta during aortic aneurysm surgeries, ischemia-reperfusion (IR) develops, and it may cause damage to aorta itself or even to remote organs by oxidative stress or inflammation. Fluoxetine (FLX) which might be used in the preoperative period for its tranquilizing effect also has antioxidant effects in short-term use. The purpose of our study is to examine whether FLX protects aorta tissue, against the damage caused by IR.

METHODS: 3 groups of Wistar rats formed randomly. 1) Control group (sham-operated), 2) IR group (60 min. ischemia+120 min. perfusion), 3) FLX+IR group (FLX dose was 20 mg/kg for 3 days i.p. before IR). At the end of each procedure, aorta samples were collected, and oxidant-antioxidant, anti-inflammatory, and anti-apoptotic status of the aorta were evaluated. Histological examinations of the samples were provided.

RESULTS: Levels of LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA were found to be significantly increased in the IR group compared to control (p<0.05) and the SOD, GSH, TAS, and IL-10 levels were significantly lower (p<0.05). FLX significantly decreased LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA levels in the FLX+IR group compared to IR group (p<0.05) and increased IL-10, SOD, GSH, and TAS (p<0.05). FLX administration prevented the deterioration of aortic tissue damage.

CONCLUSION: Our study is the first study that demonstrates FLX mediated suppression of IR injury in the infrarenal abdominal aorta by antioxidant, anti-inflammatory, and anti-apoptotic properties.

Keywords

Main Subjects

References

1. Kim GS, Ahn HJ, Kim WH, Kim MJ, Lee SH. Risk factors for postoperative complications after open infrarenal abdominal aortic aneurysm repair in Koreans. Yonsei Med J 2011; 52: 339-346.
2. Zammert M, Gelman S. The pathophysiology of aortic cross-clamping. Best Pract Res Clin Anaesthesiol 2016; 30: 257-269.
3. Prata MP, Jaldin RG, Lourencao P, Sobreira ML, Yoshida RA, Terra SA, et al. Acute aortic wall injury caused by aortic cross-clamping: morphological and biomechanical study of the aorta in a swine model of three aortic surgery approaches. J Vasc Bras 2020; 19: e20190025.
4. Guner I, Yaman MO, Aksu U, Uzun D, Erman H, Inceli M, et al. The effect of fluoxetine on ischemia-reperfusion after aortic surgery in a rat model. J Surg Res 2014; 189: 96-105.
5. Aksu U, Guner I, Yaman OM, Erman H, Uzun D, Sengezer-Inceli M, et al. Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model. Journal of Physiology and Biochemistry 2014; 70: 925-934.
6. Yaman OM, Erman H, Guner I, Tok OE, Pala M, Esrefoglu M, et al. Remote myocardial injury: the protective role of fluoxetine. Canadian Journal of Physiology and Pharmacology 2018; 96: 319-327.
7. Ferrari RS, Andrade CF. Oxidative Stress and lung ischemia-reperfusion injury. Oxid Med Cell Longev 2015; 2015: 590987.
8. Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW, et al. Current Mechanistic Concepts in Ischemia and Reperfusion Injury. Cell Physiol Biochem 2018; 46: 1650-1667.
9. Yang B, Fung A, Pac-Soo C, Ma D. Vascular surgery-related organ injury and protective strategies: update and future prospects. Br J Anaesth 2016; 117 Suppl 2: ii32-ii43.
10. Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull 2004; 70: 71-86.
11. Seal JB, Gewertz BL. Vascular dysfunction in ischemia-reperfusion injury. Ann Vasc Surg 2005; 19: 572-584.
12. Halladin NL. Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries. Dan Med J 2015; 62: B5054.
13.Wong DT, Bymaster FP, Engleman EA. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: Twenty years since its first publication. Life sciences 1995; 57: 411-441.
14. Zafir A, Ara A, Banu N. In vivo anti-oxidant status: A putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 220-228.
15. Behr GA, Moreira JC, Frey BN. Preclinical and clinical evidence of anti-oxidant effects of antidepressant agents: implications for the pathophysiology of major depressive disorder. Oxid Med Cell Longev 2012; 2012: 609421.
16. Alboni S, Poggini S, Garofalo S, Milior G, El Hajj H, Lecours C, et al. Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. Brain Behav Immun 2016; 58: 261-271.
17. Caiaffo V, Oliveira BD, de Sa FB, Evencio Neto J. Anti-inflammatory, antiapoptotic, and anti-oxidant activity of fluoxetine. Pharmacol Res Perspect 2016; 4: e00231.
18. Kirkova M, Tzvetanova E, Vircheva S, Zamfirova R, Grygier B, Kubera M. Anti-oxidant activity of fluoxetine: studies in mice melanoma model. Cell Biochem Funct 2010; 28: 497-502.
19. Sinay L, Kurthy M, Horvath S, Arato E, Shafiei M, Lantos J, et al. Ischaemic postconditioning reduces peroxide formation, cytokine expression and leukocyte activation in reperfusion injury after abdominal aortic surgery in rat model. Clin Hemorheol Microcirc 2008; 40: 133-142.
20. Aksu U, Guner I, Yaman OM, Erman H, Uzun D, Sengezer-Inceli M, et al. Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model. J Physiol Biochem 2014; 70: 925-934.
21. Yaman OM, Erman H, Guner I, Tok OE, Pala M, Esrefoglu M, et al. Remote myocardial injury: the protective role of fluoxetine. Can J Physiol Pharmacol 2018; 96: 319-327.
22. Li C, Wang Z, Li X, Chen J. Effects of semicarbazide-sensitive amine oxidase inhibitors on morphology of aorta and kidney in diabetic rats. BMC Endocr Disord 2019; 19: 59-Last page.
23. Kruger NJ. The bradford method for protein quantitation. Methods Mol Biol 1994; 32: 9-15.
24. Soares ROS, Losada DM, Jordani MC, Evora P, Castro ESO. Ischemia/reperfusion injury revisited: An overview of the latest pharmacological strategies. Int J Mol Sci 2019; 20: Pages.
25. Nemmar A, Al-Salam S, Beegam S, Yuvaraju P, Ali BH. Aortic Oxidative Stress, Inflammation and DNA Damage Following Pulmonary Exposure to Cerium Oxide Nanoparticles in a Rat Model of Vascular Injury. Biomolecules 2019; 9: Pages.
26. Brigelius-Flohe R, Flohe L. Regulatory phenomena in the glutathione peroxidase superfamily. Anti-oxid Redox Signal 2020; 33: 498-516.
27. Pal SN, Dandiya PC. Glutathione as a cerebral substrate in depressive behavior. Pharmacol Biochem Behav 1994; 48: 845-851.
28. Kolla N, Wei Z, Richardson JS, Li XM. Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide. J Psychiatry Neurosci 2005; 30: 196-201.
29. Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an active disease biomarker: Recent biochemical and pathological perspectives. Med Sci (Basel) 2018; 6: Pages.
30. Lee JY, Kim HS, Choi HY, Oh TH, Yune TY. Fluoxetine inhibits matrix metalloprotease activation and prevents disruption of blood-spinal cord barrier after spinal cord injury. Brain 2012; 135: 2375-2389.
31. Lim CM, Kim SW, Park JY, Kim C, Yoon SH, Lee JK. Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res 2009; 87: 1037-1045.
32. Zhao Y, Shang P, Wang M, Xie M, Liu J. Neuroprotective effects of fluoxetine against chronic stress-induced neural inflammation and apoptosis: Involvement of the p38 activity. Front Physiol 2020; 11: 351-Last page.
33. Liu FY, Cai J, Wang C, Ruan W, Guan GP, Pan HZ, et al. Fluoxetine attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage: a possible role for the regulation of TLR4/MyD88/NF-kappaB signaling pathway. J Neuroinflammation 2018; 15: 347-Last page.
34. Liu T, Zhang L, Joo D, Sun SC. NF-kappaB signaling in inflammation. Signal Transduct Target Ther 2017; 2: Pages.
35. Greijer AE, van der Wall E. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol 2004; 57: 1009-1014.
36. Djordjevic J, Djordjevic A, Adzic M, Elaković I, Matić G, Radojcic MB. Fluoxetine affects anti-oxidant system and promotes apoptotic signaling in Wistar rat liver. European journal of pharmacology 2011; 659: 61-66.
37. Reus GZ, Abelaira HM, Agostinho FR, Ribeiro KF, Vitto MF, Luciano TF, et al. The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain. J Psychiatr Res 2012; 46: 1029-1035.
38. Katseni K, Chalkias A, Kotsis T, Dafnios N, Arapoglou V, Kaparos G, et al. The Effect of Perioperative Ischemia and Reperfusion on Multiorgan Dysfunction following Abdominal Aortic Aneurysm Repair. Biomed Res Int 2015; 2015: 598980.
39. Wang X, Khalil RA. Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease. Adv Pharmacol 2018; 81: 241-330.
40. Teder P, Heldin P. Mechanism of impaired local hyaluronan turnover in bleomycin-induced lung injury in rat. Am J Respir Cell Mol Biol 1997; 17: 376-385.
41. Sieve I, Munster-Kuhnel AK, Hilfiker-Kleiner D. Regulation and function of endothelial glycocalyx layer in vascular diseases. Vascul Pharmacol 2018; 100: 26-33.
42. Stair-Nawy S, Csoka AB, Stern R. Hyaluronidase expression in human skin fibroblasts. Biochem Biophys Res Commun 1999; 266: 268-273.
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 3
March 2023
Pages 301-307

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