Evaluation of the Preventive Role of two Mn-salen Complexes in Induction of Steatohepatitis in Rats

Nonalcoholic steatohepatitis (NASH), a stage of fatty liver, occuring in individuals with little or no alcohol consumption, is characterized by macro- and microvesicular steatosis with inflammation, ballooning degeneration, hepatocyte necrosis, Mallory bodies and fibrosis. It has been suggested that oxidative stress might play an important role in the pathog­enesis and progress of NASH. The aim of present study was to determine the preventive effect of catalytic antioxidants (two Mn-salen complexes) on diet-induced steatohepatitis in rats. NASH was induced in male N-Mary rats by feeding them with a methionine - choline deficient (MCD) diet for 14 weeks. The rats were randomly assigned to receive vitamin C, EUK-8, EUK-134 (n=5, 30 mg/Kg/day) or vehicle orally. At the end of the experiment, sera biochemical analyses and histopathological examination of liver samples were performed. Treatment of rats with Mn-salens and or vitamin C significantly reduced the sera cholesterol, glucose, aminotransferases and alkaline phosphatase activities, the extent of lipid peroxidation and protein carbonylation whereas the weight and HDL level were significantly increased. In addition, these compounds improved NASH pathological features in liver of MCD fed rats. SPSS statistical software was used for statistical analysis, with P values of less than 0.05 being considered statistically significant. Based on the present data, supplementation of Mn-salen complexes could be beneficial in the prevention of nonalcoholic steatohepatitis in rats.