Heuer Rachael M, Falagan-Lotsch Priscila, Okutsu Jessica, Deperalto Madison, Koop Rebekka R, Umeh Olaedo G, Guevara Gabriella A, Noor Md Imran, Covington Myles A, Shelton Delia S
University of Miami.
Auburn University.
Res Sq. 2024 Jul 3:rs.3.rs-4583781. doi: 10.21203/rs.3.rs-4583781/v1.
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 (). 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.
心血管疾病是一种猖獗的公共卫生威胁。环境污染物,如有毒金属镉(Cd),已被证明与心血管疾病风险增加有关。鉴于人类接触镉的情况随着时间的推移而增加,因此需要开发新的疗法来改善镉的毒性。硒(Se)是一种必需的微量元素,已被提议用于挽救镉毒性的影响,但效果不一。硒的治疗窗口狭窄,需要精确给药以避免毒性。在这里,我们使用斑马鱼评估了各种水体中镉和硒的浓度及顺序对心脏功能的影响。我们发现镉以浓度依赖的方式诱导心包水肿并改变心率。为了确定硒对镉诱导的心脏毒性的治疗范围,在暴露于2.5和5μg/L的镉之前,将斑马鱼胚胎用0、10、50、100、150或200μg/L的硒处理1-4天。我们发现,在2.5μg/L的镉之前进行50μg/L的硒预处理,但在5μg/L的镉之前则不然,可降低斑马鱼心包水肿的发生率并改善镉诱导的心动过缓。暴露于10和50μg/L硒的胚胎显示出典型的心脏形态,而其他暴露于硒和缺硒的鱼则出现心包水肿。更长的硒预处理时间导致心包水肿的发生率更低。总体而言,本研究强调了优化硒浓度和预处理时间以发挥其对镉诱导的心脏毒性的保护作用的重要性。这些发现为减少人类镉相关心血管损伤的潜在治疗策略提供了见解。