Taurine protects rat testes against NaAsO(2)-induced oxidative stress and apoptosis via mitochondrial dependent and independent pathways.
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.
Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, West Bengal, India.
Joydeep
J
Das
Jyotirmoy
J
Ghosh
Prasenjit
P
Manna
Mahua
M
Sinha
Parames C
PC
Sil
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000633:toxicity*; D004347:Drug Interactions; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000633:toxicity*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013654:Taurine / Q000494:pharmacology*; D013733:Testicular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000975:Antioxidants; D018053:Arsenites; D017670:Sodium Compounds; D014409:Tumor Necrosis Factor-alpha; D013654:Taurine; D013739:Testosterone; C017947:sodium arsenite