The effects of environmental fluoroquinolones on the motor system in zebrafish: Reversible?

Abstract

Fluoroquinolones (FQs) are prevalent in aquatic ecosystems, posing potential environmental risks. While clinical doses of FQs are known to cause severe musculoskeletal and neurological effects in children, the severity, duration, and reversibility of their effects on motor function remain unclear. In response to these concerns, this study investigated the impact of four widely encountered FQs—ciprofloxacin, norfloxacin, ofloxacin, and levofloxacin—on zebrafish. Firstly, to evaluate the severity and duration of FQ exposure effects, we assessed locomotor activity and histopathology. Zebrafish embryos were exposed to environmental levels of FQs. Results showed significant reductions in swimming distance and activity by half in FQ-exposed zebrafish at 14 days post-fertilization (dpf). Additionally, increased myofiber size and cartilage ratios were observed in norfloxacin- and ofloxacin-exposed adult zebrafish (120 dpf). Furthermore, biomarker analysis revealed decreased creatine kinase and myoglobin contents, as well as increased Sox9 expression, indicating disrupted cartilage development. To further explore the severity and reversibility of FQ effects, we examined acute high-dose levofloxacin exposure in juvenile zebrafish (28 dpf). Significant decreases were observed in the total distance, single muscle fiber area, cartilage proportion, and content of Sox9. Locomotor activity and cartilage morphology were assessed across different recovery periods, with markers returning to normal 14 days after exposure. Overall, our findings suggest that both chronic low-dose and acute high-dose FQ exposure led to motor system toxicity in zebrafish, highlighting potential ecological risks.