Abstract
Cobalt is an essential heavy metal that is necessary for the formation of vitamin B12 (hydroxocobalamin). However, exposure to excess cobalt for a prolonged period can harm the human body, causing pulmonary fibrosis, blindness, deafness, and peripheral neuropathy. 3-Aminotriazole (3-AT) is a catalase inhibitor that is often used to investigate the physiological effects of catalase. The present study found that injection of 3-AT in mice significantly reduced CoCl2-induced hearing impairment. In cultured organ of Corti explants from rats, 3-AT treatment protected hair cells from CoCl2-induced cytotoxicity. To determine the mechanism by which 3-AT protected from CoCl2-induced ototoxicity, we used the HEI-OC1 auditory cell line. Pretreatment with 10 mM 3-AT attenuated CoCl2-induced accumulation of ROS and induction of proinflammatory cytokine expression. Interestingly, these protective effects of 3-AT did not require catalase activity, as demonstrated by a series of experiments using RNA interference-mediated catalase knockdown in HEI-OC1 cells and using catalase-deficient mouse embryonic fibroblasts. Our results demonstrated the mechanisms of CoCl2-induced ototoxicity that may provide better ways to prevent the ototoxic effect of cobalt exposure.
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Acknowledgments
This work was supported by the two National Research Foundation of Korea (NRF) Grants funded by the Korean government (MSIP): (2011-0030718) and (2014M3A9D8034463).
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The authors declare that they have no conflict of interest.
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Joon No Lee and Seul-Gi Kim have contributed equally to this study.
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Lee, J.N., Kim, SG., Lim, JY. et al. 3-Aminotriazole protects from CoCl2-induced ototoxicity by inhibiting the generation of reactive oxygen species and proinflammatory cytokines in mice. Arch Toxicol 90, 781–791 (2016). https://doi.org/10.1007/s00204-015-1506-9
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DOI: https://doi.org/10.1007/s00204-015-1506-9