Effect of nitric oxide inhibition on rat liver ischemia reperfusion injury

Abstract

Objective: To determine the role of nitric oxide (NO) in rat liver ischemia reperfusion we examined the effects of competitive NO synthesis inhibitor L-nitro-arginine-methyl-ester (L-NAME) and NO precursor L-arginin. Methods: 46 Sprague-Dawley rats were divided into five groups. Group 1, sham operated; group 2, 30-min ischemia administered; group 3, 60-min reperfusion administered after ischemia; group 4, 50 mg/kg L-NAME was given i.v. immediately before reperfusion; group 5, 50 mg/kg L-NAME + 250 mg/kg L-arginin was given i.v. immediately before reperfusion. At the end of the experiment, liver was removed and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were measured, transaminases SGOT and SGPT were measured in sera. Liver was also evaluated histopathologically. Results: Transaminase levels were the highest in ischemia reperfusion group. Transaminases in this group were high compared with sham, ischemia, L-NAME and L-arginin groups (***P > 0.001, ***P > 0.001, *P > 0.05, *P > 0.05 respectively). SOD activity was 29.8 + 4 U/mg protein in L-arginin group. This level was the lowest level in all groups. SOD activity in L-arginin group was lower than that of sham and ischemia reperfusion groups (**P > 0.01, *P > 0.05, respectively). There were no significant differences in catalase activity and MDA levels among groups. Tissue damage was significant in ischemia and ischemia reperfusion groups. Tissue damages in these groups were greater than that of sham group (***P > 0.001). In L-NAME treated group, tissue damage was similar to sham group, and significantly less than ischemia reperfusion group and L-arginin group (**P > 0.01). Conclusion: Even though there was significant tissue damage, we have not observed oxidative stress in the length of ischemia reperfusion period that we have performed. Mechanism of this damage seems to be independent from lipid peroxidation. NO supplementation decreased SOD, but did not cause further tissue damage. NO may dispose O2/- by formation of peroxynitrite. L-NAME did not change lipid peroxidation, but clearly reduced reperfusion injury