INFLUENCE OF INOSINE GLYCYL-CYSTEINYL-GLUTAMATE DISODIUM ON THE CLINICAL COURSE AND OUTCOME OF THE EXPERIMENTAL ALCOHOL-INDUCED LIVER CIRRHOSIS

Abstract

An evaluation of the inosine glycil-cysteinyl-glutamate disodium efficacy as a means for therapy of toxic alcoholinduced liver cirrhosis was performed in experiments on outbred white rats. Experimental modeling of liver cirrhosis was carried out by administrating intragastrically to rats two hepatotoxicants– 40% ethanol at a dose of 3 g/kg, every other day for three weeks and 1% dimethylnitrosamine at a dose of 5 mg/kg, intraperitoneally the first 4 days per week. Inosine glycyl-cysteinyl-glutamate disodium was administered subcutaneously at a dose of 30 mg/kg daily for three weeks; application of the drug was started after the administration of hepatotoxicants was ended and clinical and morphological indicators of toxic liver cirrhosis were proved. Evaluation of the efficiency of inosine glycyl-cysteinyl-glutamate disodium as a therapeutic means for alcohol-induced liver cirrhosis was performed by morphological, histological and biochemical methods. It was found out that a combined action of ethanol and dimethylnitrosamine led to the development of toxic liver cirrhosis, which manifested by an increase in the rats body weight , characteristic morphological and histological changes in liver tissues, increased activity of alanine and aspartate aminotransferase, gamma-glutamyltranspeptidase, alkaline phosphatase and total bilirubin level, and an increase in the blood plasma of concentration of interleukin-1β, interferon-γ and tumor necrosis factor-α. A course administration of inosine glycyl-cysteinyl-glutamate disodium contributed to a decrease in the volume of connective tissue in the liver of animals, decrease in the activity of hepatic enzymes, decrease in the level of total bilirubin and the concentration of pro-inflammatory cytokines in the blood plasma. Data obtained show the efficacy of inosine glycyl-cysteinyl-glutamate disodium as a means for treating alcohol-induced liver cirrhosis.