Insights into the combined toxicity of copper and cadmium in zebrafish (Danio rerio) embryos and adults

Metal pollution poses a persistent environmental challenge, impacting both ecosystems and human health. While efforts have been made to understand the mechanisms underlying the toxicological outcomes of metal pollution, there remains insufficient understanding of the key molecular and physiological events in co-exposure scenarios and across different life stages. We investigated the toxic effects of copper (0.80 μM Cu) and cadmium (0.25 μM Cd), both individually and in combination, on zebrafish (Danio rerio) embryos and adults. Key morphological and functional endpoints were assessed in embryos at 96 hours post-fertilisation (hpf) and in adults after seven days of exposure. Metal accumulation and molecular responses related to oxidative stress, apoptosis, metal transport, and DNA damage were studied at both life stages to gain insights into general and specific stress responses. The results show increased sensitivity of both embryos and adult animals to the co-exposure compared to single metal exposures. Embryos displayed higher vulnerability compared to adults. Oxidative stress emerged as a common mechanism of toxicity across both life stages, albeit with distinct defensive responses. Our results challenge the simplified assumption that metal accumulation alone can predict toxicity, highlighting the necessity of considering internal metal dynamics and physiological resilience. Investigations into other metal combinations and their effects on diverse species are warranted to fully elucidate the complexities of mixture toxicity in organisms.