Assessing the toxicity of bongkrekic acid in zebrafish embryos

Bongkrekic acid (BA) is a potent bacterial toxin found in certain fermented foods, which poses a serious risk to human health through rapid multi-organ failure. Its toxic effects on the early stage of vertebrates remain poorly understood. In this study, we addressed this gap using zebrafish embryos as a model to evaluate BA's developmental toxicity. Following 96-h exposure to BA at concentrations of 0.01, 0.05, 0.1, and 1 mg/L, mortality rates increased sharply between 0.05 mg/L (25 %) and 0.1 mg/L (79 %). Morphological assessments at BA concentrations ≥0.1 mg/L revealed significant reductions in body length, eye and lens areas, and otic vesicle and otolith areas, as well as an enlarged yolk sac, indicating disrupted development and impaired nutrient utilization. Concentrations of BA of ≥0.05 mg/L induced bradycardia, hypo-contractility, and a larger ventricular volume, indicative of cardiotoxicity. BA at ≥0.05 mg/L reduced response rates in sensorimotor assessments and decreased neuromast hair cell numbers, suggesting neurobehavioral impairment. BA at ≥0.1 mg/L also induced hepatotoxicity, marked by reductions in liver area and EGFP fluorescence, along with signs of metabolic acidosis. Additionally, reductions in the mitochondrial-rich ionocyte density at ≥0.1 mg/L suggested compromised ion regulation. A histopathological examination revealed damage to critical organs, including the brain, eyes, and liver. These findings illustrate BA's multifaceted toxicity in embryos, impacting cardiac, neurobehavioral, liver metabolic, and ion regulatory functions.