Chloroxylenol causes cardiovascular toxicity and neurobehavioural abnormalities by inducing mitochondrial dysfunction and oxidative stress in zebrafish (Danio rerio).

Chloroxylenol (PCMX), a commonly used antibacterial agent, has been detected in diverse water environmental samples and living organisms, posing potential risks to ecosystems and human health. However, its potential impact on aquatic organisms remains poorly understood. In this study, we investigated the effects of PCMX on embryonic development, cardiovascular system, neurobehaviour, and the underlying mechanisms in zebrafish embryos exposed to concentrations of 0, 0.4, 1.2, 2, 2.8, 5.2, 7.6, and 10 mg/L until 120 h post-fertilisation (hpf). Our results demonstrated that PCMX reduced the developmental rate of zebrafish embryos, delayed hatching, and caused morphological abnormalities. Furthermore, PCMX exposure caused severe cardiovascular defects and impaired cardiac function, as evidenced by dysregulated expression of genes related to cardiovascular development. These cardiovascular impairments may be linked to behavioural changes observed in the larvae. Mechanistic studies revealed that the inhibition of genes involved in the mitochondrial respiratory chain complex disrupted oxidative phosphorylation (OXPHOS), resulting in excessive production of reactive oxygen species (ROS) and increased oxidative stress. ROS accumulation further caused mitochondrial damage and triggered apoptosis through the mitochondrial pathway. Additionally, aberrant expression of calcium signalling pathway genes indicated that PCMX may impair cardiac development and function by disrupting calcium transport. In summary, PCMX exposure induced cardiovascular toxicity and neurobehavioural disorders by causing mitochondrial dysfunction, increasing oxidative stress, and triggering apoptosis via the mitochondrial pathway. These findings provide new insights into the impact of PCMX on the development of aquatic organisms and the potential risks to human health.