Hepatotoxicity, developmental toxicity, and neurotoxicity risks associated with co-exposure of zebrafish to fluoroquinolone antibiotics and tire microplastics: An in silico study

J Hazard Mater. 2024 Dec 15:485:136888. doi: 10.1016/j.jhazmat.2024.136888. Online ahead of print.

Abstract

This study aimed to investigate the differences in the mechanisms of microscopic hepatotoxicity, developmental toxicity, and neurotoxicity in aquatic organisms co-exposed to styrene-butadiene rubber tire microplastics (SBR TMPs) and fluoroquinolone antibiotics (FQs). We found that hepatotoxicity in zebrafish induced by SBR TMPs and FQs was significantly higher than developmental toxicity and neurotoxicity. Furthermore, the main effects of the FQs primarily manifested as synergistic toxicity, whereas the low- and high-order interactions of the FQs mainly exhibited synergistic and antagonistic effects, respectively. Factorial analysis and the mixture toxicity index revealed that the synergistic effects of lomefloxacin × moxifloxacin and ciprofloxacin × lomefloxacin × enrofloxacin interactions significantly contributed to hepatotoxicity in zebrafish exposed to SBR TMP. SBR TMPs and antibiotics primarily induced hepatotoxicity, developmental toxicity, and neurotoxicity in zebrafish by affecting the activities of Cyp1a, Acox1, TRα, and mAChR. The observed toxicities were closely linked to the hydrophilic/hydrophobic groups, electronegativity, group mass, and structural complexity of the FQ molecules. This study provides new insights regarding the toxicological risks to aquatic organisms from co-exposure to SBR TMPs and FQs from a microscopic perspective. Future studies should include a broader range of antibiotics and tire microplastics and consider their long-term adverse effects on aquatic life.

Keywords: Adverse outcome pathway; Aquatic toxicity; Fluoroquinolone antibiotics; Quantitative structure-activity relationship model; Tire microplastics.