THE ROLE OF OXIDATIVE STRESS IN DOXORUBICIN-INDUCED LIVER INJURY IN RATS WITH NONALCOHOLIC STEATOHEPATITIS

Maslova G. S.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Determining the role of oxidative stress in the detoxification and regenerative liver function violation is of particular importance in order to optimize the prevention of hepatotoxic reactions during chemotherapy (CT). The aim – to investigate the effect of oxidative stress on arginase and ornithine decarboxylase (ODC) activity in liver tissues in rats with anthracycline-induced toxic hepatitis depending on nonalcoholic steatohepatitis (NASH) presence. Object and methods. The studies were performed on 30 white nonlinear adult rats, of which 15 (50%) males, 15 (50%) females, weighing 160-220 g. Experimental animals were divided into 3 groups: I (n=10) – rats with NASH, that received intraperitoneally doxorubicin 5 mg/kg/day with a cumulative dose of 15 mg/kg; II (n=10) – rats without NASH, that were administered doxorubicin similarly to group I; III (n=10) – rats without NASH, that received 0.9% sodium chloride solution 1 ml for 3 days. The TBA reactive substances, catalase, arginase and ODC were determined in the liver homogenate. Study results. In rats of group I with NASH, the doxorubicin appointment led to an increase in the concentration of TBA reactive substances in 3.9 times while the catalase activity decreased in 1.9 times in the liver homogenate compared to control (p<0.05). Activation of free radical production in group I rats was accompanied by a decrease in arginase activity in 1.6 times and ODC in 1.8 times in liver homogenate compared to control (p<0.05). An inverse correlation was found in rats of group I between the content of TBA reactive substances and arginase activity (r=- 0.76; p<0.05). In rats without NASH, doxorubicin administration resulted in a 2.6-fold increase in the concentration of TBA reactive substances in the liver homogenate without disturbances in the antioxidant defense system (p<0.05), which was associated with an inhibition of arginase activity in 1.7 times compared to controls. An inverse correlation was found in group II rats between the content of TBA reactive substances and arginase activity (r=-0.71; р<0.05). Conclusions. The doxorubicin administration is accompanied by oxidative stress, which against the background of NASH leads to impaired detoxification and regenerative liver function.

doxorubicin, oxidative stress, arginase, ornithine decarboxylase, nonalcoholic steatohepatitis.

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«Bulletin of problems biology and medicine» Issue 2 (156), 2020 year, 128-132 pages, index UDK 616.36-0,02:599.323.4

10.29254/2077-4214-2020-2-156-128-132