Mechanism of immunotoxicological effects of tributyltin chloride on murine thymocytes

作者：Sharma Neelima^*; Kumar Anoop

来源：Cell Biology and Toxicology, 2014, 30(2): 101-112.

DOI：10.1007/s10565-014-9272-7

• Apoptosis
• Apoptosis-inducing factor
• Calcium
• Caspase
• Endonuclease G
• Tributyltin

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 G(1) 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 Ca2+ 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.

• 出版日期2014-4