Taurine protects rat testes against NaAsO(2)-induced oxidative stress and apoptosis via mitochondrial dependent and independent pathways

Toxicol Lett. 2009 Jun 22;187(3):201-10. doi: 10.1016/j.toxlet.2009.03.001. Epub 2009 Mar 14.

Abstract

Arsenic (As) is a well known toxicity inducer. Recent investigations, however, showed that it might have some therapeutic application in cancer treatment. These dual roles of arsenic have attracted a renewed research in organ pathophysiology. In this study, we report that As administration (in the form of NaAsO(2) at a dose of 10mg/kg body weight for 2 days, orally) induces apoptosis in testicular tissue of the experimental rats by the activation of caspase-3 and reciprocal regulation of Bcl-2/Bad with the concomitant reduction of mitochondrial membrane potential and increased level of cytosolic cytochrome C. Arsenite has also been shown to induce activation of mitogen-activated protein kinases (MAPKs), Akt as well as NF-kappaB (p65) in testicular tissue. In addition, As significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities and reduced the plasma testosterone level, testicular sperm count and sperm motility. Besides, arsenite exposure increased the levels of reactive oxygen species (ROS), serum TNF-alpha, As accumulation and lipid peroxidation and decreased the activities of the antioxidant enzymes and glutathione in the testicular tissue. Oral administration of taurine (at a dose of 100mg/kg body weight for 5 days) was found to be effective in counteracting As-induced oxidative stress, attenuation of testicular damages and amelioration of apoptosis in testicular tissue by controlling the reciprocal regulation of Bcl-2/Bad, phospho-ERK1/2, phospho-p38, phospho-Akt and NF-kappaB. Taurine was also found to play similar beneficial role via mitochondrial dependent pathways in As-induced testicular damages leading to apoptotic cell death.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Arsenites / toxicity*
  • Drug Interactions
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Sodium Compounds / toxicity*
  • Sperm Count
  • Sperm Motility / drug effects
  • Taurine / pharmacology*
  • Testicular Diseases / chemically induced*
  • Testicular Diseases / metabolism
  • Testicular Diseases / pathology
  • Testicular Diseases / prevention & control
  • Testis / drug effects
  • Testis / metabolism
  • Testosterone / blood
  • Testosterone / metabolism
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antioxidants
  • Arsenites
  • Sodium Compounds
  • Tumor Necrosis Factor-alpha
  • Taurine
  • Testosterone
  • sodium arsenite