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脱氢醋酸钠诱导斑马鱼钙失衡相关的心血管毒性。

Sodium dehydroacetate induces cardiovascular toxicity associated with Ca imbalance in zebrafish.

机构信息

College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Centers for Disease Control and Preventative Medical Research, Beijing 100013, China.

College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.

出版信息

Ecotoxicol Environ Saf. 2021 Jan 15;208:111613. doi: 10.1016/j.ecoenv.2020.111613. Epub 2020 Nov 9.

DOI:10.1016/j.ecoenv.2020.111613
PMID:33396133
Abstract

The environmental effects of additives have attracted increasing attention. Sodium dehydroacetate (DHA-S), as an approved preservative, is widely added in processed foods, cosmetics and personal care products. However, DHA-S has been recently reported to induce hemorrhage and coagulation aberration in rats. Yet little is known about the ecotoxicological effect and underlying mechanisms of DHA-S. Here, we utilized the advantage of zebrafish model to evaluate such effects. DHA-S induced cerebral hemorrhage, mandibular dysplasia and pericardial edema in zebrafish after 24 h exposure (48-72 hpf) at 50 mg/L. We also observed the defective heart looping and apoptosis in DHA-S-treated zebrafish through o-dianisidine and acridine orange staining. Meanwhile, DHA-S induced the deficiency of Ca and vitamin D3 in zebrafish. We further demonstrated that DHA-S stimulated Ca influx resulting in Ca-dependent mitochondrial damage in cardiomyocytes. Additionally, DHA-S inhibited glucose uptake and repressed the biosynthesis of amino acids. Finally, we identified that sodium bicarbonate could rescue zebrafish from DHA-S induced cardiovascular toxicity. Altogether, our results suggest that DHA-S is a potential risk for cardiovascular system.

摘要

添加剂的环境影响引起了越来越多的关注。脱氢乙酸钠(DHA-S)作为一种批准使用的防腐剂,广泛应用于加工食品、化妆品和个人护理产品中。然而,DHA-S 最近被报道会导致大鼠出血和凝血异常。然而,关于 DHA-S 的生态毒理学效应及其潜在机制知之甚少。在这里,我们利用斑马鱼模型的优势来评估这种效应。DHA-S 在 50mg/L 浓度下,暴露于斑马鱼 24 小时(48-72 hpf)后,会导致斑马鱼出现脑出血、下颌骨发育不良和心包水肿。我们还通过邻联茴香胺和吖啶橙染色观察到 DHA-S 处理的斑马鱼存在心脏环化缺陷和细胞凋亡。同时,DHA-S 会导致斑马鱼体内钙和维生素 D3 缺乏。我们进一步证明 DHA-S 会刺激钙内流,导致心肌细胞中钙依赖性线粒体损伤。此外,DHA-S 会抑制葡萄糖摄取并抑制氨基酸的生物合成。最后,我们发现碳酸氢钠可以挽救 DHA-S 引起的斑马鱼心血管毒性。总的来说,我们的研究结果表明,DHA-S 可能对心血管系统有潜在的风险。

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