Structure-dependent visual toxic mechanisms of benzothiazoles in zebrafish larvae (Danio rerio).

Vision serves as the primary sensory function for most animals and is essential for their survival. Benzothiazoles (BTs) are widely used in various industrial applications and can be frequently detected in various environmental media. However, current understanding of their visual toxicity remains limited. In the present study, three typical BTs, 2-mercapto-benzothiazole (MBT), 2-hydroxy-benzothiazole (2-OH-BTH), and 2-amino-benzothiazole (2-ABTH), were chosen to explore the visual toxicity and mechanisms in zebrafish larvae. The results showed that all of the three BTs inhibited eye development and suppressed optokinetic response in larvae. The damages induced by 2-ABTH and 2-OH-BTH could be attributed to the oxidative stress and the over activation of GABAergic signaling, respectively, while MBT exerted toxic effects through both pathways. Density functional theory calculation showed that MBT and 2-ABTH possessed high reactivity than 2-OH-BTH, which provided a potential explanation for their higher potency to induce oxidative stress. In addition, molecular docking and molecular dynamics simulation showed that MBT and 2-OH-BTH can form stable complexes with Gabrb3, which could be responsible for the enhanced GABAergic signaling. These findings provide new insights into the distinct visual toxic mechanisms of BTs underlying their subtle structural differences.