Transcriptional Responses in Adult Zebrafish (Danio rerio) Exposed to Propranolol and Metoprolol.

Abstract

β-adrenergic receptor blockers (β-blockers) are widely detected in the aquatic environment; however, the effects of these pharmaceuticals on aquatic organisms remain uncertain. In this study, adult zebrafish were exposed to two different β-blockers, propranolol and metoprolol, for 96h. After exposure, the transcriptional responses of genes encoding the β-adrenergic receptor (i.e., adrb1, adrb2a, adrb2b, adrb3a and adrb3b), genes involved in detoxification and the stress response (i.e., hsp70, tap, mt1 and mt2), and genes related to the antioxidant system (i.e., cu/zn-sod, mn-sod, cat and gpx) were examined in the brain, liver and gonad. Our results show that both propranolol and metoprolol exposure changes the mRNA level of β-adrenergic receptors, indicating clear pharmacological target engagement of the β-blockers. The transcription of genes related to antioxidant responses and detoxification process were induced, suggesting that β-blocker exposure can activate the detoxification process and result in oxidative stress in fish. Moreover, the transcriptional responses displayed substantial tissue- and gender-specific effects. Considering the environmental concentrations of propranolol and metoprolol, these results suggest that these pharmaceuticals are unlikely to pose a risk to fish. However, the impacts in prolonged exposure, along with other possible side effects due to β-adrenergic receptor blockade, should be further assessed.