The necessity to minimize adverse effects of tuberculosis chemotherapy requires a comprehensive evaluation of the effects of antituberculosis drugs on the reproductive system and testicular cell macromolecules. The epidemiological situation of tuberculosis in Central and Eastern Europe is getting worse. Data on adverse effects of antituberculosis drugs are scare concerning particularly their effects on the reproductive system. The aim of the present study was to investigate the potential effect of ethambutol, rifampicin, isoniazid and pyrazinamide co-administration on lipid peroxidation, glutathione content and protein SH-groups, DNA fragmentation levels, the reproductive capacity of Wistar male rats and the antenatal development of their posterity. The rats (150–170 g) were divided into two groups: group I – received antituberculosis drugs suspended in 1% starch gel per os: ethambutol – 155 mg/kg b.w./day, rifampicin – 74.4 mg/kg b.w./day, isoniazid – 62 mg/kg b.w./day, pyrazinamide – 217 mg/kg b.w./day, group II (control) – received only starch gel in corresponding volumes. The contents of TBA-active compounds, glutathione and protein SH-groups in testis and sperm were determined spectrophotometrically, the DNA-fragmentation was determined using an UV transilluminator (BIORAD, USA), reproductive system indices were measured by standard methods. The co-administration of therapeutic doses of ethambutol, isoniazid, rifampicin and pyrazinamide to male rats during the period of spermatogenesis caused an increase in the rate of thiobarbituric acid reactive substances formation in testis and sperm, decrease of testis glutathione and protein SH-group contents, significant changes in DNA fragmentation, fatal decrease of male fertilizing capacity and fertility, and increase of pre- and post-implantation embryo lethality. The changes in reproductive indices could be the result of direct or indirect effects of one or more drugs investigated.
Objectives:To investigate the effects of diabetes on the reproductive system and extracellular matrix proteins of diabetic rats. Materials and Methods: Wistar albino male rats, body weight (BW) 160-200 g, were divided into two groups: Istreptozoticin diabetes, IInormal non-diabetic animals. The content of amino acids in rat type I collagen was determined using an amino acid analyzer. Morphological analyses of gonadic structures were carried out by an optic microscope. Results: The study of the effects of diabetes on type I collagen amino acid content, testis cells morphologic and morphometric parameters and spermatogenesis demonstrated the presence of diabetes-mediated quantitative and qualitative changes in male rat reproductive organs, spermatogenetic epithelial cells and extracellular matrix proteins in comparison with normal. Conclusions: Observed collagen molecules changes could hence affect the properties and correct functioning of spermatogenetic epithelium and of other tissues of reproductive organs. They could be caused by diabetes via deficiency of insulin which is involved in collagen synthesis regulation at different stages of this process, cytochrome P450-2E1 induction and reactive oxygen species effects on protein biosynthesis processes.
This study is a complex investigation of alcohol-mediated changes in CYP2E1 mRNA and protein expression in the testes, as well as spermatogenesis indices and type I collagen amino acid contents, in male rats. Wistar albino male rats were divided into two groups: I -control (intact animals), II -experimental (chronic alcoholism, exposure to a 15 % ethanol aqueous solution during 150 days). The destructive changes in the spermatogenic epithelium were accompanied by a decrease in sperm number and motility time. CYP2E1 mRNA and protein expression were elevated in the testes 3 and 1.4 times, respectively. Also, signifi cantly lower contents of lysine, glutamic acid, serine, proline, alanine, valine, and phenylalanine residues accompanied by an increase of hydroxyproline, glycine, and threonine residue contents were detected in the skin type I collagen of the experimental group. Chronic ethanol consumption caused testicular failure along with an overexpression of CYP2E1 mRNA and protein in the testes as well as quantitative changes in type I collagen amino acid contents. The profound alcohol-mediated changes in collagen type I amino acid contents may have affected the spermatogenic epithelium state. The modulation of testicular cytochrome P450 2E1 mRNA and protein expression could change the functioning of this isozyme in target organs and take part in the mechanism of ethanol gonadotoxicity.
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