Experimental justification choise to prevent hepatotoxic reactions to anti-TB drugs based on gene-phenotypic characteristics

To prevent the progression of hepatotoxic reaction in newly diagnosed patients with tuberculosis, various drugs of many groups are used. A benchmark assessment of the hepatoprotective effect of ropren, essentiale forte, ursosan, and heptral for rats with different acetylation phenotypes with liver damage caused by anti-tuberculosis drugs (ATD). Rats with a different acetylation phenotype were given the isoniazid, rifampicin, pyrazinamide, ethambutol daily for 2 weeks administered simultaneously with one of the hepatoprotectors: ropren, essentiale, ursodeoxycholic acid, ademetionin. The administration of the ATD led to the increase of biochemical markers in comparison with the normal ones of the intact rats. When using ropren, esentiale forte, ademetionine “fast acetylators” had ALT decrease to the norm activity level, and when using ursosan and heptral - AST. When using ropren and essentiale “slow acetylators” had ALT activity been normalized, and only when using essentiale - AST. The bilirubins decreased to a normal level after using ademetionine and ursodeoxycholic acid in case of “fast acetylators”, and after using ropren and essentiale in case of “slow acetylators”. According to morphological criteria, decrease of dystrophic phenomena of “fast acetylators” was noticed when using ademetionine. In case of “slow acetylators” when using ropren and ursodeoxycholic acid. In order to prevent hepatotoxic reactions, it is important to conduct genetic studies to identify mutations of the enzyme genes responsible for the metabolism of ATD. If the risk of reaction - use a hepatoprotector depending on the phenotype of acetylation and the changes of biocimical markers.