Studies on characteristics of liver injury model induced by rifampicin and isoniazid in mice / 中国药理学通报

ABSTRACT

Aim: To establish an ideal anti-tuberculosis drug induced liver injury model and provide a suitable animal model for its pharmacodynamic evaluation. Methods To explore the contribution rate and interaction of isoniazid (INH) and rifampicin (RIF) on liver injury, mice received intragastric administration of RIF 100 nig · kg-1, 300 mg · kg-1 once, or RIF 300 mg · kg-1, INH 150 mg · kg-1, and RIF 300 mg · kg-1 + INH 150 mg · kg-1 for 1 -3 weeks. Then the biochemical and pathological indexes were determined and analyzed by factorial design ANOVA. Results After single intragastric administration of rifampicin, the serum bilirubin levels gradually increased, but no other indicators were affected in mice. Continuous intragastric administration of RIF 300 mg · kg-1, INH 150 mg · kg-1 or RIF 300 mg · kg-1 +INH 150 mg · kg-1 for 1 ∼3 weeks could significantly increase the liver index of mice. RIF alone or combined with isoniazid could significantly increase the level of ALT, AST and TBIL, resulting in vacuolar lesions in liver tissues in mice. The analysis of variance demonstrated that the combined use of RIF and INH for two weeks or three weeks showed significant antagonism in liver index and the level of ALT, and marked antagonism in TBIL at three weeks. The pathological results were basically consistent with the biochemical indicators. Conclusions RIF is the leading cause of liver injury in mice, and its hepatotoxicity is related to cholestasis. INH has a significant antagonistic effect on liver toxicity of RIF when they are combined, and the deep action mechanisms remains to be further explored.