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.
Keywords: 3-Aminotriazole; Cobalt; Ototoxicity; Proinflammatory cytokines; Reactive oxygen species.