The Beneficial Effect Of Melatonin And Pentoxifylline In Hepatic Ischemia And Reperfusion Injury In Rats

Objective To investigate the effect of melatonin (MT) and pentoxifylline (PTX) in hepatic ischemia and reperfusion in rats.Methods Total hepatic ischemia was induced for 35 minutes by clamping the hepatic artery, the portal vein, and the bile duct using a microvascular clamp. 128 rats were divided into four groups randomly. In group A (control group, n=32), normal saline was used through caudal vein. In group B (MT-treated group), MT was administered (10mg/kg, i.p.) at 75 and 30 min before ischemia, again just at the start of reperfusion, and after 60 and 120 min of reperfusion. In group C (PTX-treated group), PTX was given (50mg/kg, i.v.) Ih before laparotomy. In group D (PTX+MT group), PTX and MT were used together as above. Serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and tumor necrosis factor- (TNF- ) were determined. Liver tissues were taken for determination of malondialdehyde (MDA) levels, superoxide dismutase (SOD) levels, nitrite oxide (NO), endothelin-1 (ET-1). Expression of P-selectin and inductive NO synthase (iNOS) were evaluated immunohistochemistry. Seven-day survival rates were monitored.Results At 2h, 4h of reperfusion , ALT, LDH and TNF-a in group B, C, D decreased compared with group A (P<0.01), and there were significant differences between three indexes of group D and group B, C (P<0.05). At 4h of reperfusion, SOD of liver tissue in group D were significant lower than in group A. MDA and NO of liver tissue in B, D group were significantly decreased compared with group A, C. ET-1 activity were higher in group A than in group B, C, D. iNOS expression of group B, D were less severe than group A, C. Moreover, P-selectin staining was attenuated in A, C group compared with B, D group.One-week survival rates were 41.7% for control, 50% for MT, 75% for PTX and combined group.Conclusion: Considering the dosages used, MT appeared to be significantly more potent than PTX in reversing the oxidative damage induced by I;R. PTX reduced reperfusion injury of the liver through significantly decreased secretion of cytokines. Our findings show that MT and PTX have beneficial effects against I;R injury and due to their synergistic effects, when administered in combination, may have a more pronounced protective effects on the liver.