Oxidative Stress and Apoptosis of Adult Zebrafish ( <i>Danio rerio</i> ) Liver Exposed to Tire Wear Particle (TWP) Leachates

Tire wear particles (TWPs) and their leachates are a source of microplastic pollution and are toxic to aquatic organisms. However, their specific hepatotoxicity in zebrafish and the underlying mechanisms remain poorly understood. This study employed zebrafish models in a semistatic toxicity experiment to examine hepatic ecological toxicity following exposure to various concentrations of TWP leachates (1.7%, 3.4%, and 8.5%) over 7, 14, 21, and 28 days. The results showed that changes in superoxide dismutase (SOD), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) content in zebrafish liver led to oxidative stress, lipid peroxidation, and DNA damage, and TWP leachates also affected concentration- and time-dependent gene expression changes, with the severity increasing with concentration. Molecular docking confirmed Zn2+ in TWP leachates induced hepatotoxicity by binding to Cu/Zn-SOD (model score of 0.96). QSAR toxicity predictions identified significant developmental toxicity for 4-tert-butylphenol and 3-tert-butyl-4-hydroxyanisole, with scores of 0.79 and 0.88, respectively. The increased acetylcholinesterase (AChE) activity, along with the molecular binding of the two compounds to the enzyme (with binding energies of −5.3 and −5.24 kcal/mol, respectively), collectively demonstrates their neurotoxicity and reveals the integrated toxicity mechanism of TWP leachates.