Exposure of Zebrafish (danio Rerio) to Clioquinol Reveals Embryological and Developmental Toxicity

Clioquinol (CQ) belongs to the 8-hydroxyquinoline family of antimicrobial agents. In the 1970s, CQ was withdrawn from the market due to reported neurotoxicity in humans. Although oral use was discontinued, topical formulations for treating fungal and parasitic infections remained available. With the potential reintroduction of oral CQ formulations for novel indications, a comprehensive understanding of its toxicity is essential. Thus, this study aimed to investigate the embryonic developmental toxicity of CQ in zebrafish. Embryos were exposed to concentrations of 0.1, 0.5, 1.0, 1.5, and 2.0 μg/ml of CQ for 168 hours, during which physiological, morphological, and behavioral parameters were assessed. Results indicate that CQ exhibited toxicity, causing 100% mortality within the first 48 hours at concentrations of 1.5 and 2.0 μg/ml. Additionally, a delay in hatching rate was observed after 72 hours of exposure to 1 μg/ml, and morphological abnormalities were evident at lower concentrations. Furthermore, exploratory behavior was evaluated in 7-day-old post-fertilization larvae exposed to the lowest CQ concentration, where severe morphological alterations were not observed. Exposure to CQ at 0.1 µg/ml led to altered swimming patterns, suggesting possible locomotor damage induced by CQ exposure. In conclusion, this study is the first to demonstrate the potential embryotoxicity of CQ in zebrafish, highlighting the importance of understanding the toxicity profile before considering its reintroduction for oral use.