Toxic Effects Of Beta-Adrenergic Receptor Antagonist On The Mode Fish

Beta-adrenergic receptor antagonists (so called "beta-blocks") are considered as one class of emerging environmental contaminants in the aquatic environment. Because beta-blocks are widely detected in the aquatic environment and are biologically active, the ecotoxicological effects of beta-blockers on non-target organisms (particularly fish) must be of concern. In this study, the embryo development toxicity and larvae acute toxicity of two representative beta-blockers, i.e. non-selective β-blocker propranolol and β1-selective blocker metoprolol, were evaluated on zebrafish and Japanese medaka. Moreover, the transcriptional responses of genes involved in the various physiological processes, including antioxidant, detoxification and apoptosis, as well as which related with adrenergic system, were determined in zebrafish larvae exposed to two beta-blockers at sublethal concentrations. Also, the transcriptional levels of genes were determined in the liver, gonad and brain of adult zebrafish following exposure to two beta-blockers, and the gender or tissue specific toxicity of beta-blockers on teleost was explored. Additionally, since both beta-blockers are chiral, the enantioselectivity was assessed after comparing the toxicity on fish exposed to each enantiomer. The results showed that both compounds caused acute toxicity on larvae, and resulted in the increase of embryo mortality, the decrease of hatchling rate and heart rate, in a concentration-dependent manner. Consistent with the pharmaceutical mechanism of beta-blocker, heart rate might be served as a potential biomarker for these pharmaceutical chemicals. The transcriptional responses demonstrated that the exposure of beta-blockers changed the transcriptional level for some genes with obvious gender or tissue specificity. No enantioselectivity was observed by physiological indicators, whereas difference transcriptional responses were found between two enantiomers. The data of this research will be helpful for improving the risk assessment for these pharmaceuticals.