title: Comparative investigation of methionine and novel formulation Metovitan protective effects in Wistar rats with testicular and epididymal toxicity induced by anti-tuberculosis drugs co-administration.
abstract: Despite clear beneficial effects, studies on the efficacy of different formulations of micronutrients and vitamins in the treatment of male infertility are still very limited. The aim of the study was to compare the efficacy of methionine and novel formulation Metovitan based on the combination of methionine, thiamine, nicotinamide, α-tocopherol acetate and zinc salt as remedies for prevention of anti-tuberculosis drugs (ATD) anti-fertility effects in male rats. ATD co-administration resulted in testicular CYP2E1, CYP2C23 and CYP3A2 transcriptional activation. Methionine and Metovitan regulated the level of CYP2E1 and CYP3A2 mRNA expression. Methionine unaffected CYP2C23 mRNA level, while Metovitan effectively normalized this parameter. The use of methionine did not allow normalizing of DNA fragmentation processes in testes, while Metovitan provided decrease in the number of DNA fragments to the control level. Both substances significantly decreased p-nitrophenol hydroxylase activity and prevented pro/antioxidant parameters imbalance in testes of ATD-treated rats. The end results of methionine and Metovitan application were partial or complete restoration of altered spermatogenesis parameters with subsequent increase in sperm count and fertility. Ameliorating effects may be attributed to antioxidant properties and modulating effects on testicular CYPs. More pronounced beneficial Metovitan effects might be due to synergic effects of its components.
authors.affiliation: General Toxicology Department, SI «Institute of Pharmacology & Toxicology NAMS of Ukraine», Eugene Pottier Str. 14, Kyiv, Ukraine. Electronic address: anna_shayakhmetova@yahoo.com.
authors.forename: Ganna M
authors.initials: GM
authors.lastname: Shayakhmetova
authors.affiliation: General Toxicology Department, SI «Institute of Pharmacology & Toxicology NAMS of Ukraine», Eugene Pottier Str. 14, Kyiv, Ukraine.
authors.forename: Larysa B
authors.initials: LB
authors.lastname: Bondarenko
authors.affiliation: General Toxicology Department, SI «Institute of Pharmacology & Toxicology NAMS of Ukraine», Eugene Pottier Str. 14, Kyiv, Ukraine.
authors.forename: Alla K
authors.initials: AK
authors.lastname: Voronina
authors.affiliation: General Toxicology Department, SI «Institute of Pharmacology & Toxicology NAMS of Ukraine», Eugene Pottier Str. 14, Kyiv, Ukraine.
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Kovalenko
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004338:Drug Combinations; D004822:Epididymis / Q000187:drug effects* / Q000473:pathology; D007248:Infertility, Male / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008715:Methionine / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology
chemical_list: D000995:Antitubercular Agents; C000717351:Cyp2c23 protein, rat; D004338:Drug Combinations; D003577:Cytochrome P-450 Enzyme System; D008715:Methionine; D000090762:Cytochrome P-450 CYP2J2
keywords: Anti-tuberculosis drugs; CYPs; Methionine; Metovitan; Spermatogenesis; Testes