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

G Shayakhmetova

doi:10.17721/1728_2748.2016.72.80-85

Abstract

Comparative study of anti-tuberculosis drugs anti-androgenic effects and effects on testicular CYP2E1 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.

Highlights

The epidemiological situation of tuberculosis in the world keeps worsening [1]
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
It is well known that both toxic intermediates and reactive oxygen species (ROS) overproduction take place during CYP2E1-mediated xenobiotics metabolism [8]

Summary

Introduction

All patients from countries with a known high incidence of resistant M. tuberculosis strains, all patients who had been treated previously, and all patients with life-threatening tuberculosis, receive as initial anti-tuberculosis therapy the same combination of isoniazid (INH), rifampin (RMP) and pyrazinamide (PZA), together with at least one additional medicine (ethambutol (EMB) and/or streptomycin) [2]. In such situation investigation of these compounds adverse effects becomes of vitally importance. It is well known that both toxic intermediates (which are able to interact with vitally important cells structures) and reactive oxygen species (ROS) overproduction (with the further development of oxidative stress) take place during CYP2E1-mediated xenobiotics metabolism [8]

Methods

Results

Conclusion