Therapeutic Efficacy of Selenium Pre-treatment in Mitigating Cadmium-Induced Cardiotoxicity in Zebrafish (Danio rerio).

ABSTRACT

Cardiovascular diseases are a rampant public health threat. Environmental contaminants, such as Cadmium (Cd), a toxic metal, have been linked to increased risk for cardiovascular diseases. Given that human exposure to Cd is increasing overtime, there is a need to develop new therapies to ameliorate Cd toxicity. Selenium (Se), an essential trace element, has been proposed to rescue the effects of Cd toxicity, with mixed effects. Se's narrow therapeutic window necessitates precise dosing to avoid toxicity. Here, we assessed the effects of various waterborne Cd and Se concentrations and sequences on cardiac function using zebrafish (Danio rerio). We showed that Cd induced pericardial edemas and modified heart rates in a concentration-dependent manner. To identify the therapeutic range of Se for Cd-induced cardiotoxicity, zebrafish embryos were treated with 0, 10, 50, 100, 150, or 200 µg/L Se for 1-4 days prior to exposure to Cd at 2.5, and 5 µg/L. We found that a 50 µg/L Se pre-treatment prior to Cd at 2.5 µg/L, but not at 5 µg/L, reduced the prevalence of pericardial edemas and ameliorated Cd-induced bradycardia in zebrafish. Embryos exposed to 10 and 50 µg/L of Se showed typical heart morphology, whereas other Se-exposed and Se-deficient fish presented pericardial edemas. Longer Se pre-treatment durations led to fewer incidences of pericardial edemas. Overall, this study highlights the importance of optimizing Se concentration and pre-treatment periods to harness its protective effects against Cd-induced cardiotoxicity. These findings provide insights into potential therapeutic strategies for reducing Cd-related cardiovascular damage in humans.