Toxic effects of four cardiovascular drugs on the development and epigenetics of zebrafish (Danio rerio).

Due to the prevalence of cardiovascular diseases, therapeutic drugs such as atenolol (ATE), metoprolol (MET), atorvastatin (ATO), and bezafibrate (BZB) have been widely used and thus frequently detected in surface water at ng·L-1-µg·L-1 level. In this study, the developmental toxicity of these drugs (0.5 µg·L-1-500 µg·L-1) to zebrafish, an aquatic model organism, was investigated; and the epigenetic toxicity of BZB was also explored. For all four drugs, the results showed that the drugs exposure could cause sublethal toxic effects on zebrafish larvae, such as decreases in hatching rate, body length, and heart rate. ATO also induced the swelling of the eyes of larvae by 5 %-15 %. Yolk sac edema, pericardial edema, bent spine, and tail malformation were observed in larvae exposed to the drugs, and yolk sac edema was the most common malformation. In addition, the spontaneous movement and free-swimming activity could be inhibited by the drugs. Combined with RNA-seq results, the adverse development of larvae in exposure groups may be caused by the disruption of lipid and carbohydrate metabolism, and the development and function of eye and nervous system. After a 30-day uptake period, the accumulation of BZB and the decrease of global DNA methylation level were observed in the liver, kidneys, gut, gills, and brain of adult zebrafish (4-month-old) exposed to 0.5 µg·L-1 to 500 µg·L-1 BZB. The liver was the main organ for BZB accumulation and the occurrence of DNA hypomethylation. In the liver, overexpression (1.5-7.6 times) of genes related to lipid metabolism (PPARα), DNA methylation (Dnmt1), and apoptosis (p53) was also observed. The results of the current study suggest that long-term exposure to low-concentrations of cardiovascular drugs may pose significant threats to aquatic ecosystems.

Stability of 28 typical prescription drugs in sewer systems and interaction with the biofilm bacterial community.

Identifying the attenuation characteristics of drugs in sewage and sewers is one of the important factors to improve the accuracy of wastewater-based epidemiology (WBE) application. In this study, 28 drugs including antidepressants, cardiovascular drugs, antihistamines, anticonvulsants and some of their human metabolites were chosen as the targets to study the hydrolysis, adsorption, and biodegradation at different temperatures in sewage and sewers. The interaction between drugs degradation and community structure of biofilm was also investigated. In the simulated sewers, the removal percentages of 12 parent or drug metabolites are 0-20%, such as demethylvenlafaxine, fluvoxamine, etc., which are highly stable chemicals and suitable to be chosen as biomarkers for WBE back-calculation under appropriate circumstances. Fourteen drugs including venlafaxine and citalopram have removal percentages of 20-60%. While paroxetine and sertraline, with removal percentage of 100%, are the most unstable and cannot be used as biomarkers. Among the 28 drugs, there are 25 drugs that have a higher loss rate in the aerobic sewer than that in the anaerobic sewer in this study. During drug exposure in anaerobic biofilms, species abundance first decreased and then increased. Species abundance and diversity in aerobic biofilm generally showed a decreasing trend. In addition, Proteobacteria and Spirochaetota were the dominant phyla in both sewers.