Mechanisms Underlying Tralopyril-Induced Olfactory Dysfunction in Marine Medaka: Disruption of the Dopaminergic System and the Complement Alternative Pathway

Tralopyril is an emerging antifouling biocide widely used in hull coatings. However, tralopyril is neurotoxic and a potential olfactory toxicant. Additionally, it is not easily biodegradable and poses a threat to nontarget aquatic organisms. In this study, marine medaka were exposed to environmentally relevant concentrations of tralopyril from the embryonic stage for 180 days. Olfactory behavior was assessed, and histopathological damage to the olfactory epithelium, olfactory bulb, and brain was observed. The results showed impaired olfactory behavior, thickening of the olfactory epithelium, and an increase in damaged cells and tissue vacuolation in both the olfactory bulb and brain. Measurement of cAMP levels, ion channel protein activity, and related gene expression in the olfactory epithelium indicated disruption of the olfactory signal transduction pathway. Further proteomic analysis of the brain revealed abnormalities in the complement and coagulation cascades, with a significant inhibition of the complement alternative pathway. Brain neurotransmitter-targeted metabolomics showed abnormalities in dopamine synthesis and metabolism, with a significant reduction in dopamine content. ELISA analysis also confirmed decreased C3 and dopamine levels in the olfactory epithelium. Finally, supplementation with exogenous LPS partially restored olfactory function, suggesting that the complement alternative pathway and dopamine synthesis/metabolism are potential mechanisms underlying tralopyril-induced olfactory toxicity.