M Ediz SARIHAN, Hakan PARLAKPINAR, Alaattin POLAT, Nigar VARDI, ONURAL ÖZHAN, HACI AHMET ACET

Beneficial effects of melatonin on acetylsalicylic acid induced liver damage in rats

We investigated the effects of acute high doses of acetylsalicylic acid (ASA) on liver tissue and the protective and therapeutic effects of melatonin on ASA related damage. Forty rats were randomly divided into five groups of eight: group 1, control; group 2, administered 200 mg/kg ASA; group 3, administered 5 mg/kg melatonin 45 min before ASA; group 4, administered 5 mg/kg melatonin 45 min after ASA; group 5, administered 5 mg/kg melatonin. We measured malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), myeloperoxidase (MPO) aspartate aminotransferase (AST) and alanine transaminase (ALT) in the liver. ASA treatment significantly increased MDA and MPO production, whereas it significantly decreased levels of SOD, CAT, GPx and GSH in the liver. Melatonin significantly decreased MDA and MPO production, whereas it caused increased levels of antioxidants. AST and ALT levels were higher after ASA treatment, whereas these levels were reduced significantly after melatonin administration. Our histopathological findings, including apoptosis, were consistent with the biochemical results. Melatonin exhibits beneficial effects against high dose ASA induced hepatotoxicity

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1. Voelker M, Hammer M. Dissolution and pharmacokinetics of a novel micronized aspirin formulation. Inflammo pharmacology. 2012;20(4):225-31.

2. Hersh EV, Moore PA, Ross GL. Over-the-counter analgesics and antipyretics: a critical assessment. Clin Ther. 2000;22(5):500-48.

3. Schrör K. 100 years of successful drug discovery. The history of aspirin. Pharm Unserer Zeit. 2009;38(4):306-13.

4. Gaspari F, Perico N, Locatelli M, Corna D, Remuzzi G, Garattini S. Renal handling of aspirin in the rat. J Pharmacol Exp Ther. 1989;251(1):295-304.

5. Al-Nasser IA. Salicylate-induced kidney mitochondrial permeability transition is prevented by cyclosporin A. Toxicol Lett. 1999;105(1):1-8.

6. Goel A, Chang DK, Ricciardiello L, Gasche C, Boland CR. A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells. Clin Cancer Res. 2003;9(1):383-90.

7. Dikshit P, Chatterjee M, Goswami A, Mishra A, Jana NR. Aspirin induces apoptosis through the inhibition of proteasome function. J Biol Chem. 2006;281(39):29228-35.

8. Nadanaciva S, Aleo MD, Strock CJ, Stedman DB, Wang H, Will Y. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes. Toxicol Appl Pharmacol. 2013;272(2):272-80.

9. Durak I, Karaayvaz M, Cimen MY. Aspirin impairs antioxidant system and causes peroxidation in human erythrocytes and guinea pig myocardial tissue. Hum Exp Toxicol. 2001;20(1):34–7.

10. Kesik V, Lenk MK, Kurekci AE. Do zinc and selenium prevent the antioxidant, hepatic and renal system impairment caused by aspirin in rats? Biol Trace Elem Res. 2008;123(1-3):168-78.

11. Nakagawa M, Ishihara N, Shimokawa T, Kojima S. Effect of colifibrate on lipid peroxidation in rats treated with aspirin and 4-pentenoic acid. J Biochem. 1987;101(1):81-8.

12. Aebi HE. Catalase in vitro. Methods Enzymol. 1984;105:121-6.

13. Zhang X, Ouyang J, Thung SN. Histopathologic manifestations of druginduced hepatotoxicity. Clin Liver Dis. 2013;17(4):547-64.

14. Sahna E, Parlakpinar H, Vardi N, Ciğremis Y, Acet A. Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats. Acta Histochem. 2004;106(5):331-6.

15. Parlakpinar H, Acet A, Gul M, Altinoz E, Esrefoglu M, Colak C. Protective effects of melatonin on renal failure in pinealectomized rats. Int. J. Urol. (2007);14: 743-748.

16. Watson RR. Melatonin in the promotion of health, 2nd edition. CRC Press, Florida. 2012;355.

17. Mizrak B, Parlakpinar H, Acet A, Turkoz Y. Effects of pinealectomy and exogenous melatonin on rat hearts. Acta Histochem. 2004;106(1):29-36.

18. Fadillioglu E, Kurcer Z, Parlakpinar H, Iraz M, Gursul C. Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus. Arch Pharm Res. 2008;31(6):705-12.

19. Silva SO, Rodrigues MR, Carvalho SR, Catalani LH, Campa A, Ximenes VF. Oxidation of melatonin and its catabolities, N1-acetyl-N2-formyl5-methoxykynuramine, N1-acetyl-5-methoxykynuramine, by activated leukocytes. J Pineal Res. 2004;37(3):171-5.

20. Onuki J, Almedia EA, Medeiros MH, Di Mascio P. Inhibition of 5-aminolevulinic acid-induced DNA damage by melatonin, N1-acetylN2-formyl-5-methoxykynuramine, quercetin or resveratrol. J Pineal Res. 2005;38(2):107-15.

21. Didolkar AK, Patel PB, Roychowdhury D. Effect of aspirin on spermatogenesis in mature and immature rats. Int J Androl. 1980;3(5):585-93.

22. Colak C, Parlakpinar H. Hayvan Deneyleri: in vivo denemelerin bildirimi: ARRIVE kılavuzu-Derleme. J Turg Ozal Med Cent. 2012;19(2):128-31.

23. Livio M, Benigni A, Zoja C. Differential inhibition by aspirin of platelet thromboxane and renal prostaglandins in the rat. J Pharmacol Exp Ther. 1989;248(1):334-41.

24. Uzbay T, Parlakpinar H, Akdag E, Celik T, Yararbas G, Ulusoy G, Acet A, Kose A, Kayir H. Chronic melatonin treatment reverses disruption of prepulse inhibition in pinealectomized and pinealectomized-plus-ovariectomized rats. Behav Brain Res. 2013;239:1-7.

25. Wei H, Frenkel K. Relationship of oxidative events and DNA oxidation in Sencar mice to in vivo promoting activity of phorbol ester-type tumor promoters. Carcinogenesis. 1993;14(6):1195-201.

26. Parlakpinar H, Orum MH. The antioxidant effect of melatonin on myocardial ıschemia reperfusion ınjury in experimental studies. Med Science. 2014;3(4):1766-80.

27. Colak C, Parlakpinar H, Ozer MK, Sahna E, Cigremis Y, Acet A. Investigating the protective effect of melatonin on liver injury related to myocardial ischemia-reperfusion. Med Sci Monit. 2007;13(11):BR251-254.

28. Lien YH, Lai LW, Silva AL. Pathogenesis of renal ischemia/reperfusion injury: lessons from knockout mice. Life Sci. 2003;74(5):543-52.

29. Raza H, John A, Benedict S. Acetylsalicylic acid-induced oxidative stress, cell cycle arrest, apoptosis and mitochondrial dysfunction in human hepatoma HepG2 cells. Eur J Pharmacol. 2011;668(1-2):15-24.

30. D’Argenio G, Mazzone G, Tuccillo C. Apple polyphenol extracts prevent aspirin-induced damage to the rat gastric mucosa. Br J Nutr. 2008;100(6):1228-36.

31. Belanger PM, Desgagne M, Bruguerolle B. Temporal variations in microsomal lipid peroxidation and in glutathione concentration of rat liver. Drug Metab Disp. 1991; 19(1):241-244.

32. Parlakpinar H, Orum MH, Sagir M. Pathophysiology of myocardial ischemia reperfusion injury: a review. Med. Science. 2013;2(4):935-54.

33. Reiter RJ, Tan DX, Maldonado MD. Melatonin as an antioxidant: physiology versus pharmacology. J Pineal Res. 2005;39(2):215-6.

34. Rodriguez C, Mayo JC, Sainz RM. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2004;36(1):1-9.

35. Winiarska K, Fraczyk T, Malinska D, Drozak J, Bryla J. Melatonin attenuates diabetes induced oxidative stress in rabbits. J Pineal Res. 2006;40(2):168- 176.

36. Hardeland R, Pandi-Perumal SR, Cardinali DP. Melatonin. Int J Biochem Cell Biol. 2006;38(3):313-6.

37. Gurlek A, Celik M, Parlakpinar H, Aydogan H, Bay-Karabulut A. The protective effect of melatonin on ischemia-reperfusion (I/R) injury in the groin (inferior epigastric) flap model in rats. J Pineal Res. 2006;40(4):312-7.

38. Altintas R, Polat A, Parlakpinar H, Vardi N, Beytur A, Oguz F, Sagir M, Yildiz A, Duran ZR. The effect of melatonin on acetylsalicylic acid-induced kidney and testis damage. Hum Exp Toxicol. 2014;33(4):383-95.

39. Sun Y, Yang J, Wang LZ, Sun LR, Dong Q. Crocin attenuates cisplatininduced liver injury in the mice. Hum Exp Toxicol. 2014;33(8):855-62.