Subchronic exposure of tire wear particles leachate induces oxidative stress and DNA damage in zebrafish (Danio rerio) brain

In recent years, microplastic pollution has garnered widespread attention, with tire wear particles (TWPs) being the largest source of microplastic pollution. These particles are frequently detected in aquatic environments and release various organic pollutants (such as 4-tert-Butylphenol and 3-tert-Butyl-4-hydroxyanisole(3-BHA)), potentially threatening aquatic organisms. This study hypothesized that exposure to TWPs leachate would induce brain tissue injury in zebrafish. Accordingly, after 7, 14, 21, and 28 days of continuous exposure, we investigated the ecological toxicity and mechanisms of TWPs leachate on the zebrafish brain from physiological, biochemical, and molecular perspectives. The results indicated that exposure to TWPs leachate induced varying degrees of oxidative damage and lipid peroxidation in the zebrafish brain. After 14 days of exposure, the content of 8-OHdG in the 8.5% was 19.30 times higher than the control group, signifying severe DNA damage. Moreover, significant inflammatory cell infiltration and enlarged tissue gaps were observed in the brain tissue. Acetylcholinesterase (AChE) activity increased notably, suggesting potential neurotoxic effects of TWPs leachate in zebrafish. Exposure to TWPs leachate altered the expression of antioxidant- and apoptosis-related genes in the zebrafish brain. QSAR toxicity prediction results indicated that 3-BHA and 4-tert-Butylphenol may exhibit developmental toxicity, with predicted scores of 0.88 and 0.79, respectively. Furthermore, molecular docking analyses suggested that these two compounds may interact with antioxidant enzymes (SOD), providing supportive evidence for their potential involvement in oxidative stress. These results are important for assessing the toxicological effects of TWPs leachate and exploring its mechanisms of toxicity in aquatic organisms.