Using a high-throughput zebrafish embryo screening approach to support environmental hazard ranking for cardiovascular agents.

Cardiovascular agents are among the most frequently prescribed pharmaceuticals worldwide. They are widely detected in aquatic ecosystems, while their ecotoxicological implications are rarely explored. Here, by the use of a new developed high-throughput zebrafish embryo screening approach, we systematically assessed the cardiovascular disruptive effects of 32 commonly used cardiovascular agents at environmental relevant concentrations and above (0.04, 0.2 and 1 µM). Multiple endpoints, including cardiac output, heart rate and blood flow, were quantified via customized video analysis approaches. Among the 32 agents, simvastatin and lovastatin exhibited the strongest toxicities to fish embryos, and the lethal doses were observed at 0.2 µM and 1 µM. Beta-blockers such as atenolol and metoprolol significantly decreased heart rates by up to 15% and 12% and increased blood flows by up to 14% and 14%, respectively, at concentrations as low as 0.04 µM. Several hypertension/hyperlipidemia medications such as pravastatin and enalapril led to significant inhibition of heart rates (up to 14% and 16% decreases, respectively) as well as slightly decreases of the cardiac outputs and blood flows. In addition, a tentative risk assessment clearly demonstrated that some compounds such as atenolol, metoprolol and bezafibrate pose considerable risks to aquatic organisms at environmental or slightly higher than surface water concentrations. Our results provided novel insights into understanding of the potential risks of cardiovascular agents and contributed to their environmental hazard ranking.