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

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Cardiovascular Toxicology Pub Date : 2024-11-01 Epub Date: 2024-08-30 DOI:10.1007/s12012-024-09910-0
Rachael M Heuer, Priscila Falagan-Lotsch, Jessica Okutsu, Madison Deperalto, Rebekka R Koop, Olaedo G Umeh, Gabriella A Guevara, Md Imran Noor, Myles A Covington, Delia S Shelton
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Abstract

Cardiovascular diseases are a rampant public health threat. Environmental contaminants, such as Cadmium (Cd), a toxic metal, are risk factors for cardiovascular diseases. Given that human exposure to Cd is increasing, there is a need for 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 zebrafish larvae 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 2.5 and 5 μg/L Cd. We found that a 50 µg/L Se pre-treatment before 2.5 μg/L Cd, but not 5 μg/L Cd, reduced the prevalence of pericardial edemas and ameliorated Cd-induced bradycardia in zebrafish. Zebrafish exposed to 10 and 50 μg/L of Se for up to 4 days showed typical heart morphology, whereas other Se-exposed and control 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 concentrations 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.

Abstract Image

硒预处理在减轻斑马鱼(Danio rerio)镉诱导的心脏毒性方面的疗效
心血管疾病是一种猖獗的公共健康威胁。环境污染物,如有毒金属镉(Cd),是心血管疾病的风险因素。鉴于人类接触镉的机会越来越多,因此需要改善镉毒性的疗法。硒(Se)是一种人体必需的微量元素,有人提出用硒来缓解镉毒性的影响,但效果不一。硒的治疗窗口较窄,因此必须精确用药以避免中毒。在这里,我们利用斑马鱼(Danio rerio)评估了不同水载镉和硒浓度及序列对心脏功能的影响。我们发现,镉会诱发心包水肿,并以浓度依赖性的方式改变斑马鱼幼体的心率。为了确定 Se 对镉诱导的心脏毒性的治疗范围,我们在斑马鱼胚胎暴露于 2.5 和 5 μg/L 镉之前,分别用 0、10、50、100、150 或 200 μg/L Se 处理 1-4 天。我们发现,在斑马鱼暴露于 2.5 μg/L Cd(而非 5 μg/L Cd)之前进行 50 μg/L Se 预处理,可降低心包水肿的发生率,并改善 Cd 引起的心动过缓。暴露于 10 和 50 μg/L Se 长达 4 天的斑马鱼表现出典型的心脏形态,而其他暴露于 Se 的鱼和对照组鱼则出现心包水肿。Se 预处理时间越长,心包水肿的发生率越低。总之,这项研究强调了优化 Se 浓度和预处理期的重要性,以利用其对 Cd 诱导的心脏毒性的保护作用。这些研究结果为减少镉对人体心血管的损害提供了潜在的治疗策略。
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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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