Pesticide metabolite 3, 5, 6-trichloro-2-pyridinol causes massive damage to the cochlea resulting in hearing loss in adult mice.

Abstract

Pesticides are a group of extensively used man-made chemicals with high toxicity and strong residues, which are closely related to hearing health. Pesticide metabolite 3, 5, 6-Trichloro-2-pyridinol (TCP) exposure leads to neurotoxicity and auditory cell toxicity. However, whether TCP causes damage to hearing in adult mice is not clear. In this study, adult male C57BL/6 mice continuously exposed to TCP for 21 days showed a dose-dependent elevation of hearing threshold. Outer hair cells and spiral neuron cells were lost in a dose-dependent manner. Type I and V of spiral ligament were severely shrunk and stria vascularis were thinned in mice after 50 and 150 mg/kg TCP exposure. Similarly, ROS levels in the cochlea were significantly increased whereas the activities of anti-oxidation enzymes were decreased after TCP exposure. The expression level of Na⁺/K⁺ ATPase was decreased, resulting in cochlear potential disruption. Levels of inflammatory factors (TNF-α and IL-1β), γ-H2AX, and pro-apoptotic-related factors (Bax and cleaved-Caspase 3) were elevated, respectively. These results suggest that TCP can cause oxidative stress, inflammation, and imbalance of cochlear potential in the cochlea, induce cochlear DNA damage and apoptosis, and cause cochlear morphological changes, eventually leading to impaired hearing function.