Department of General Practice, The Affiliated Wuxi Clinical College of Nantong University, Jiangsu, China; The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2022 Dec;262:109452. doi: 10.1016/j.cbpc.2022.109452. Epub 2022 Sep 5.
5-Hydroxymethylfurfural (5-HMF) is a small molecule aldehyde compound produced by the Maillard reaction. As 5-HMF exists in a variety of foods and drugs and is easily ingested by humans, it has attracted extensive toxicological attention in recent years. Relevant research showed that 5-HMF has cytotoxicity, genotoxicity, and tumor effects. However, the cardiovascular effects of 5-HMF are unknown. To investigate the cardiovascular effects of 5-HMF in zebrafish, wild-type and transgenic embryos were treated with 10, 25, and 50 μg/mL of 5-HMF, followed by toxicological evaluation, histological observation, fluorescence observation, cell apoptosis staining, and gene quantitative analysis. High 5-HMF concentrations led to a significant increase in the heart rate and pericardial edema ratio, larger venous sinus-arterial bulb distance, more apoptosis of cardiac cells, cardiac linearization, defects in angiogenesis and cardiovascular development, and apoptosis-related gene expression disorders in zebrafish larvae. The abnormal phenotype caused by 5-HMF can be rescued by antioxidant N-acetyl-L-cysteine (NAC) and Wnt signaling pathway activator BML-284. It is inferred that high 5-HMF concentrations increased the level of reactive oxygen species, inhibited the transduction of the Wnt signaling pathway, and resulted in abnormal cardiovascular development in zebrafish larvae. This study provides a reference for understanding the mechanism of 5-HMF effects on cardiac development.
5-羟甲基糠醛（5-HMF）是一种由美拉德反应产生的小分子醛类化合物。由于 5-HMF 存在于各种食物和药物中，并且容易被人类摄入，近年来它引起了广泛的毒理学关注。相关研究表明，5-HMF 具有细胞毒性、遗传毒性和肿瘤作用。然而，5-HMF 的心血管效应尚不清楚。为了研究 5-HMF 在斑马鱼中的心血管效应，用 10、25 和 50μg/ml 的 5-HMF 处理野生型和转基因胚胎，然后进行毒理学评价、组织学观察、荧光观察、细胞凋亡染色和基因定量分析。高浓度的 5-HMF 导致心率和心包水肿比显著增加，静脉窦-动脉球距离增大，心脏细胞凋亡增加，心脏线性化，血管生成和心血管发育缺陷，以及斑马鱼幼虫中与细胞凋亡相关的基因表达紊乱。抗氧化剂 N-乙酰-L-半胱氨酸（NAC）和 Wnt 信号通路激活剂 BML-284 可挽救 5-HMF 引起的异常表型。推断高浓度的 5-HMF 增加了活性氧的水平，抑制了 Wnt 信号通路的转导，导致斑马鱼幼虫心血管发育异常。本研究为了解 5-HMF 对心脏发育影响的机制提供了参考。
