5-HMF affects cardiovascular development in zebrafish larvae via reactive oxygen species and Wnt signaling pathways

Abstract

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.