title: 3-Aminotriazole protects from CoCl2-induced ototoxicity by inhibiting the generation of reactive oxygen species and proinflammatory cytokines in mice.
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.
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Joon No
authors.initials: JN
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Seul-Gi
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Raghbendra Kumar
authors.initials: RK
authors.lastname: Dutta
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Choe
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea.
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.affiliation: Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan, Jeonbuk, Republic of Korea. rkpark@wku.ac.kr.
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D000640:Amitrole / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D003035:Cobalt / Q000633:toxicity*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods
chemical_list: D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D003035:Cobalt; D002374:Catalase; C018021:cobaltous chloride; D000640:Amitrole
keywords: 3-Aminotriazole; Cobalt; Ototoxicity; Proinflammatory cytokines; Reactive oxygen species