Introduction. Thioacetamide is an organosulfur compound widely used in industry and as a model toxicant in experiments on laboratory animals. Despite certain successes in finding ways to correct toxic changes in the liver using pharmacological agents, surgical intervention or exposure to physical factors, the effectiveness of treating liver fibrosis and cirrhosis is currently low. Purpose of the work is to evaluate the effectiveness of prophylactic correction of thioacetamide hepatotoxicity with long-term exposure. Materials and methods. The experiment were conducted over 100 days on 56 outbred conventional male rats. Thioacetamide was administered intraperitoneally twice a week at a dose of 50 mg/kg b.w. The carrier and control substance were saline. Correction was performed 1 hour before the toxicant ademetionine and a complex compound of 5-hydroxy-6-methyluracil with acetylcysteine. Biochemical, genetic, and morphological parameters were studied at periods of 50 and 100 days. Statistical analysis was performed using SPSS Statistics 21.0 software (IBM, USA). Results. When exposed to thioacetamide, the activity of the studied enzymes increased. The results of histomorphological studies at two time points of the experiment indicate the effect of thioacetamide on the rat liver to manifest in the form of mixed (postnecrotic and atrophic) cirrhosis. A tendency towards an increase in the expression of the Casp7 gene was established. Preventive administration of corrective drugs had a noticeable effect on the activity of the gamma-glutamyl transferase enzyme. Ademetionine was more effective at 50 days, and MG-10 at 100 days. With prophylactic administration of MG-10, the growth of fibrous tissue in the liver and its infiltration with leukocytes were visualized to a lesser extent. The limitations of the study are that with long-term exposure to TAA, the hepatoprotective efficacy of the drugs was assessed only for two apoptosis genes. For a more complete assessment of the effectiveness of the correction, it is necessary to compare the results with other indicators of the toxic effect of TAA. Conclusion. Thioacetamide, when administered for a long time at a dose of 50 mg/kg b.w., causes a significant hepatotoxic effect, manifested in pathological changes in biochemical, morphological, and genetic parameters. Prophylactic administration of a complex compound of oxymethyluracil with acetylcysteine has a greater hepatoprotective effect.
Repina et al. (Thu,) studied this question.