Pyrazinamide potential effects on male rats DNA fragmentation, bone type I collagen amino acid composition, reproductive capability and posterity antenatal and postnatal development

摘要

Current therapeutic regimens with first-line antitubercular agents are associated with a high rate of adverse effects which can lead to therapeutic failure. Understanding the nature and the severity of these effects is important for treatment optimization. The aim of present study was to investigate pyrazinamide potential effects on male rats DNA fragmentation, amino acid composition of bone type I collagen, reproductive capability and their posterity antenatal and postnatal development. Wistar albino male rats (160-200 g b.w.) were divided into three groups: I - received pyrazinamide per os at a dose of 1000 mg/kg b.w./day, II - at a dose of 2000 mg/kg b.w./day, in both groups it was given for 60 days; III - control. After 60 days of the experiment, rats of the experimental (groups I and II) and control groups were mated with intact virgin females. The amino acids contents of male rat bone type I collagens were determined using amino acid analyzer; epididymis and testis DNA fragmentation - electrophoretically; posterity antenatal development indices and postnatal development - by standard procedures. The study of pyrazinamide effects (administered in different doses) on males bone type I collagen amino acid contents and testis DNA fragmentation demonstrated the presence of dose-dependent pyrazinamide-mediated quantitative and qualitative changes in male rat reproductive organs DNA and extracellular matrix proteins in comparison with control. Changes in nucleic acids and proteins structure were accompanied by alterations in processes of fertilization (with intact females), embryogenesis and by lowering of posterity survival.