Toxicity and Enantiospecific Differences of Two β-blockers, Propranolol and Metoprolol, in the Embryos and Larvae of Zebrafish (Danio rerio)

摘要

The risk presented by β-blockers on aquatic organisms remains uncertain, particularly given the enantiospecific differences in toxicity of chiral β-blockers. In this study, the toxicity of two β-blockers, propranolol and metoprolol, was determined. The 96-h LC_(50) of propranolol in the zebrafish larvae was 2.48 mg/L, whereas 50 mg/L metoprolol did not result in death. Both β-blockers decreased the heart rate and hatching rate and increased the mortality of the zebrafish embryos. Among these indicators, the heart rate was the most sensitive. However, the acute larval and embryo toxicity results displayed no enantio-selectivity. Additionally, the transcriptional response of the genes encoding the β-adrenergic receptors and those involved in other physiological processes, including the antioxidant response, detoxification, and apoptosis, in zebrafish larvae exposed to the β-blockers was examined. Although the changes in gene transcription were fairly minor, significant enantioselectivity was observed for β-blockers, suggesting that the transcriptional response was more sensitive for the evaluation of enantiospecific toxicity. Based on these results, the pharmaceutical drugs were not expected to pose a risk to fish; however, this conclusion should not be considered final. These results also demonstrated that the enantiospecific toxicity of chiral β-blockers should be investigated when performing an ecological risk assessment.