title: Mechanism of immunotoxicological effects of tributyltin chloride on murine thymocytes.
abstract: Tributyltin-chloride, a well-known organotin compound, is a widespread environmental toxicant. The immunotoxic effects of tributyltin-chloride on mammalian system and its mechanism is still unclear. This study is designed to explore the mode of action of tributyltin-induced apoptosis and other parallel apoptotic pathways in murine thymocytes. The earliest response in oxidative stress followed by mitochondrial membrane depolarization and caspase-3 activation has been observed. Pre-treatment with N-acetyl cysteine and buthionine sulfoximine effectively inhibited the tributyltin-induced apoptotic DNA and elevated the sub G1 population, respectively. Caspase inhibitors pretreatment prevent tributyltin-induced apoptosis. Western blot and flow cytometry indicate no translocation of apoptosis-inducing factor and endonuclease G in the nuclear fraction from mitochondria. Intracellular Ca(2+) levels are significantly raised by tributyltin chloride. These results clearly demonstrate caspase-dependent apoptotic pathway and support the role of oxidative stress, mitochondrial membrane depolarization, caspase-3 activation, and calcium during tributyltin-chloride (TBTC)-induced thymic apoptosis.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India, nsharma@bitmesra.ac.in.
authors.forename: Neelima
authors.initials: N
authors.lastname: Sharma
authors.forename: Anoop
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D053148:Caspase 3 / Q000096:biosynthesis*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060168:Thymocytes / Q000473:pathology*; D013950:Thymus Gland / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D061945:Caspase Inhibitors; D017382:Reactive Oxygen Species; D014220:Trialkyltin Compounds; C011559:tributyltin; D019328:Buthionine Sulfoximine; D053148:Caspase 3; D003545:Cysteine; D002118:Calcium