Hepatotoxicity of Certain Drug Combinations for Treatment of Drug-Resistant Tuberculosis and Possibilities of its Prevention

The objective: comparative assessment of hepatotoxicity of combinations of anti-tuberculosis drugs (ATBDs) including those recommended for short-course chemotherapy and analysis of protective properties of Semax and ascorbigen.

Subjects and Methods. The study consisted of 2 experiments with different combinations of anti-tuberculosis drugs and the accompanying drug. In Experiment 1, rats in the experimental groups received Mxf Lzd Pto Cs Z and Mxf Lzd Pto Cs Z + Semax; in Experiment 2, they received Mxf Lzd Pto Bdq Cfz and Mxf Lzd Pto Bdq Cfz + ascorbigen. Rats in control groups were administered 1% starch gel orally. The duration of administration made 14 days in all groups. Hepatotoxicity was assessed by biochemical parameters and pathomorphological criteria.

Results. In rats, receiving Mxf Lzd Pto Cs Z, a statistically significant increase in transaminase and total bilirubin levels as well as profound changes in liver tissue were detected versus Control Group. In rats receiving Mxf Lzd Pto Bdq Cfz, despite the elevated transaminase activity, pathomorphological changes in the liver were less severe. The use of Semax and ascorbigen contributed to the improvement of enzymatic activity and lower liver tissue damage. It has been shown that the toxicity modifying properties of ascorbigen are more pronounced, however, the hepatoprotective potential of Semax was manifested when the structural liver disorders were more severe. 

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