title: Pyrazinamide-mediated changes in rat type I collagen and spermatogenesis indices.
abstract: Necessity of tuberculosis chemotherapy adverse effects minimization requires a comprehensive evaluation of the effects of antitubercular drugs on reproductive system and extracellular matrix proteins. Wistar albino male rats (160-200 g) were divided into three groups: I--received pyrazinamide per os at a dose of 1000 mg/kg bw/day, II--at a dose of 2000 mg/kg bw/day, in both group it was given for 60 days; III--intact animals. The contents of amino acids in rat type I collagens were determined using an amino acid analyzer. Morphological analyses were carried out by an optical microscope. The study of the effects of pyrazinamide administered in different doses on type I collagen amino acid contents, testis cells morphologic and morphometric parameters and spermatogenesis demonstrated the presence of pyrazinamide-mediated quantitative and qualitative changes in male rat reproductive organs, spermatogenic epithelial cells and extracellular matrix proteins in comparison with norm.The largest number of changes were established at a dose 2000 mg/kg b.w./day. The observed collagen molecules changes could hence affect the properties and correct functioning of spermatogenic epithelium and other tissues of reproductive organs. They might be caused by pyrazinamide via cytochrome P450 2E1 induction, reactive oxygen species production or direct action of this compound on protein biosynthesis processes.
authors.affiliation: SI Institute of Pharmacology & Toxicology Academy of Medical Sciences of Ukraine, Eugene Potier 14, Kyiv, 03680, Ukraine.
authors.forename: Larysa B
authors.initials: LB
authors.lastname: Bondarenko
authors.forename: Ganna M
authors.initials: GM
authors.lastname: Shayakhmetova
authors.forename: Taisiya F
authors.initials: TF
authors.lastname: Byshovets
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Kovalenko
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D024042:Collagen Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D011718:Pyrazinamide / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013076:Sperm Count; D013090:Spermatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D024042:Collagen Type I; D011718:Pyrazinamide