COMPARATIVE INVESTIGATION OF ANTI-TUBERCULOSIS DRUGS EFFECTS ON TESTICULAR CYP2Е1 EXPRESSION AND MALE REPRODUCTIVE PARAMETERS UNDER SEPARATE AND COMBINED ADMINISTRATION IN MALE RATS

Abstract

Comparative study of anti-tuberculosis drugs anti-androgenic effects and effects on testicular CYP2Е1 has been performed. Testicular CYP2E1 mRNA and protein expression, serum total testosterone level, fertility and spermatogenesis parameters in male rats under simultaneous and separate administration of ethambutol, isoniazid, rifampin and pyrazinamide have been investigated. Analysis of the obtained data has proved the prominent role of ethambutol and isoniazid in gonadal toxicity of antituberculosis drugs combination. Activation of CYP2Е1-dependent metabolizing systems in testicular steroidogenic cells could stipulate at least a part of ethambutol, isoniazid and anti-tuberculosis drugs combination negative effects on testosterone level and spermatogenesis processes. Mechanisms of spermatogenesis alteration by rifampin and pyrazinamide need to be explored more extensively, but in the light of our observations they do not depend from testicular CYP2E1.

Keywords

• anti-androgenic effects, anti-tuberculosis drugs, protein expression, ethambutol, isoniazid