CONNECTION BETWEEN CYTOCHROME P-450 mRNA ISOFORMS EXPRESSION IN TESTIS AND RAT’S FERTILITY ANDER CONDITION OF COMBINED AND SEPARATE ADMINISTRATION OF ANTITUBERCULOSIS DRUGS

Under real conditions great number of chemical agents act on organism simultaneously. Detection of their combined action on males’ reproductive system is of special importance. Aim of our study was to compare action of antitubercular drugs (ATD) — ethambutol (ET), rifampicin (R), izoniazid (IZN) and pyrazinamid under their combined and separate administration in equitherapeutic doses on CYP2Е1, CYP3А2 and CYP2С23 mRNA expression in rats’ testis, as well as to determine correlation between this parameters and sperm number. It was detected the fertility index decrease under separate administration of all ATD, but the most of all — with IZN (by 24%) and ET (by 59%). Following ATD co-administration the male fertility decreased by 84% as compared with control. It have been shown the negative correlation between cauda epididymal sperm number and CYP isoforms mRNA expression level: CYP2E1, CYP3А2, CYP2С23 with ATD co-administration; CYP2E1, CYP3А2 with ЕТ and CYP2E1 with IZN. Modulation of CYP2Е1, CYP3А2 and CYP2С23 mRNA expression and, probably, their activity could be involved into pathogenetic mechanisms of male subfertility development.