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Mechanism of immunotoxicological effects of tributyltin chloride on murine thymocytes

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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 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.

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Acknowledgments

The authors acknowledge DST for finical support in the form of DST-INSPIRE fellowship and are also grateful to Dr. Shashi khandelwal, Head, Immunotoxicity laboratory, IITR, India, for her valuable suggestions and guidance for conducting this work.

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  1. Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India

    Neelima Sharma & Anoop Kumar

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  1. Neelima Sharma
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  2. Anoop Kumar
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Correspondence to Neelima Sharma.

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Sharma, N., Kumar, A. Mechanism of immunotoxicological effects of tributyltin chloride on murine thymocytes. Cell Biol Toxicol 30, 101–112 (2014). https://doi.org/10.1007/s10565-014-9272-7

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