Abstract
Purpose: Hepatic ischemia-reperfusion injury (HIR) is a severe condition which is seen after hepatic resection procedures, hepatic arterial injury and in hepatic graft in living donor transplantation. In this study, our goal was to investigate the effect of melatonin, an INOS inhibitor and antioxidant, on the prevention of lipid peroxidation in blood and liver tissue induced by HIR.
Materials and Methods: Three groups were designed for the study. 10 Wistar Albino rats (150–200 g) were used for each group. Group A: Sham, Group B: HIR, Group C: HIR + M. No substance was given to the rats in groups A and B. Ischemia was induced with vascular clampage for 45 minutes. With declampage, reperfusion injury was induced for 30 minutes. Five minutes before reperfusion, melatonin 10mgr/kg was given intraperitoneally to Group C. Forty-five minutes after reperfusion rats were sacrificed and blood and liver tissue samples were taken. Serum and liver tissue myeloperoxidase (MPO), malondialdehyde (MDA), were measured. Histopathological examinations for liver tissue were also performed.
Results: Plasma and liver tissue MDA and MPO levels were higher in HIR group. In HIR Group (Group B) necrosis and inflammation was detected in the liver tissue. Application of melatonin decreased blood MDA levels significantly, but did not lead to a significant decrease in the tissue levels. Based on the statistical data we gathered, blood and tissue MPO levels were significantly reduced in the melatonin group (Group C) and liver histopathology was significantly improved in HIR group (Group B).
Conclusion: Our study showed that application of an antioxidant in HIR injury, led to blood and lipid peroxidation and improvement in liver functions.
Keywords:
Hepatic ischemia-reperfusion injury, melatonin, lipid peroxidation
References
1Ferdinand SI, Habib N, Mathie R. Hepatic ischemia-reperfusion injury. Am J of Surg, 2001;181:160–166.
2Langdale LA, Kajikawa O, Frevert C et al. Sustained tolerance to lipopolysaccharide after liver ischemia-reperfusion injury. Shock, 2003; 19: 553–558.
3Teoh N, Field J, Sutton J, et al. Dual role of tumour necrosis factor-alpha in hepatic ischemia-reperfusion injury. Hepatology, 2004;39: 412–421.
4Arii S, Teramoto K, Kawamura T. Current progress in the understanding of and therapeutic strategies for ischemia and reperfusion injury of the liver. J Hepatobit, Pancreat Surg., 2003; 10: 189–194.
5Kimura K, Nakaki M, Takai S. et al. Pivotal role of NF-kappa B signaling in antiCD40 induced liver injury. Hepatology, 2004;40: 1180–1189.
6Xu J, Xie J, Bao M. et al. NF-kappa B/I-kappa B pathway during ischemia rperfusion injury of rat liver. Chin Med J(Engl), 2003;116:1146–1149.
7Acuna CD, Martin M, Macias M. et al. Melatonin, mitochondria and cellular bioenergetics. J Pineal Res, 2001; 30: 65–74.
8Polat A, Emre MH. Effects of melatonin or acetylsalicylic acid on gastric oxidative stress after bile duct ligation in the rats. Gastroenterol, 2006; 41:433–439.
9Esrefoglu M, Gul M,Ates B. et al. Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats. World J Gastroenterol, 2006;12:259-264.
10Yagi K. Lipid peroxides and related radicals in clinical medicine.In:Free radicals in diagnostic medicine. Armstrong D, ed. New York: Plenum Pres, 1994:1-15.
11Golowich SP, Kaplan SD, Methods in enzymology. Vol II Inc. New York:Aca Pres, 1955:769.
12Ma W, Wang ZR, Shi L. et al. Expression of macrophage inflammatory protein-1alpha in Kupffer cells following liver ischemia or reperfusion injury in rats. World J Gastroenterol, 2006;12:3854–3858.
13Shirane K, Yamaguchi K, Koga K et al. Hepatic ischemia/reperfusion injury is prevented by a novel matrix metalloproteinase inhibitor, ONO–4817. Surgery, 2006; 139:653–664.
14Jung JY, Lee SM. The roles of Kupffer cells in hepatic dysfunction induced by ischemia/reperfusion in rats. Arch Pharm Res, 2005;28:1386–1391.
15Tsung A, Hoffmann RA, Izuishi K. et al. Hepatic ischemia/reperfusion injury involves functional TLR4 signaling in nonparenchymal cells. J Immunol, 2005; 175:7661–7668.
16Abraham E. NF-kappa B activiation. Crit Care. Med, 2000;28:100–104.
17Malhi H, Gores GJ, Lemasters JJ. Apoptosis and necrosis in the liver: a tale of two deaths?.Hepatology, 2006;43:31–44.
18Matsui N, Kasajima K, Hada M. et al. Inhibiton of NF-kappaB activation during ischemia reduces hepatic ischemia/reperfusion injury in rats. J Toxicol Sci, 2005;30:103–110.
19Antolin I, Rodriguez C, Sainz RM, et al. Neurohormone melatonin prevents cell damage; effect on gene expression for antioxidativ enzymes. FASEB J,1996;10:882–890.
20Okatani Y, Wakatsuki A, Reiter RJ, et al. Protective effect of melatonin against mitochondrial injury induced by ischemia and reperfusion of rat liver. Eur J Pharmacol, 2003; 23:469:145–152.
21Sener G, Tosun O, Sehirli AO, et al. Melatonin and NAC have beneficial effects during hepatic ischemia and reperfusion. Life Sciences, 2003;72:2707–2718.
22Aydoğan S, Yerer MB, Goktas A. Melatonin and Nitric oxide. J Endocrinol Invest, 2006;29:281–287.
23Munoz-Casarez FC, Padillo FJ, Briceno A, et al. Melatonin reduces apoptosis and necrosis induced by ishemia/reperfusion injury of the pancreas. J Pineal Res,2006;40:195–203.
24Yuji O, Akihiko W, Russel R, et al. Protective effect of melatonin against mitochondrial injury induced by ischemia and reperfusion of rat liver. Eur J Pharm,2003;469:145–152.
25Sener G, Sehirli AO, Keyer-Uysal M, et al. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. J Pineal Surg, 2002;32:120–126.
26Kaçmaz A, User Y, Sehirli O, et al. Protective effect of Melatonin against Ischemia/Reperfusion- Induced Oxidative remote organ injury in the rat. Surg Today,2005;35:744–750.
27Chen JC, Ng CJ, Chiu TF, Chen HM. Altered neutrophil apoptosis activity is reversed by melatonin in liver ischemia-reperfusion. J Pineal Res, 2003 ;34:260–264.
