S-ADEMETHIONINE EFFECT ON PATHOGENETIC MECHANISMS OF DOXORUBICIN-INDUCED LIVER INJURY IN RATS WITH NON-ALCOHOLIC STEATOHEPATITIS

Abstract

Purpose – to investigate the effect of S-ademethionine on changes in prooxidantantioxidant status and arginine/citrulline cycle during doxorubicin-induced liver injury in rats with non-alcoholic steatohepatitis. Material and methods. Studies were performed on 30 white non-linear adult rats, 15 (50%) of them were males, 15 (50%) - females, weighing 160-220 g. Rats were divided into 3 groups: I (n=10) – rats (5 males and 5 females), whom from the 1st till the 63rd day NASH was simulated, then for 3 days (from the 64th till the 66th day) doxorubicin 5 mg/ kg/day was introduced intraperitoneally reaching cumulative dose of 15 mg/kg and 0.9% sodium chloride solution 1 ml; II (n=10) – rats (5 males and 5 females), whom NASH was simulated and doxorubicin was administered similarly to group I and additionally SAMe 100 mg/kg/day intraperitoneally with a total dose of 300 mg/kg; III (n=10) – rats (5 males and 5 females), which constituted a control group. The content of TBA reactants, arginine, citrulline, catalase activity, arginase, ornithine decarboxylase (ODC) were determined in the liver homogenate. Results. Doxorubicin administration in rats with NASH led to increase of TBA-reactants content with a simultaneous decrease in catalase activity, which was accompanied by a reduction in arginase and ODC activity compared with control (p<0.05). The SAMe injection allowed to reduce the manifestations of oxidative stress, potentiated by doxorubicin, as well as to prevent disorders of detoxification and protein-synthetic liver function.