Toxicity Of Adrenergic Receptor Related Pharmaceuticals To Zebrafish

Belonging to the large rhodopsin branch of G protein coupled receptor,adrenergic receptor(AR)can produce various physiological response after epinephrine or norepinephrine binds to it,which making it the target of numerous pharmaceuticals.Because these pharmaceuticals are widely used,and are released into the aquatic environment in the form of parent compound or metabolites,the concern of their potential ecological toxicity is rising.In this study,we chose moxisylyte(MOX),an ?1-adrenergic receptor blocker,propranolol(PRO),a ?-adrenergic receptor blocker,and ractopamine(RAC),a ?-adrenergic receptor agonist,as typical adrenergic receptor related pharmaceuticals,and zebrafish as experimental animals.After the determination of embryo developmental toxicity,the changes of behavior after exposure,as well as the mechanism for neurotoxicity,were studied.Moreover,since the cardiovascular system was considered as the main effector organ of adrenergic receptor related pharmaceuticals,the cardiotoxicity on zebrafish larvae was assessed.The results showed that MOX exposure(1-625 ?g/L)can prolong time to hatching,increase gross abnormality rate,while the exposure of PRO and RAC with the same concentration caused increased gross abnormality rate or prolonged time to hatching,respectively.For the locomotor behavior of exposed larvae,the swimming speed significantly increased after MOX exposure.In PRO-treated group,the swimming speed increased slightly at the lowest concentration,while decreased with the increase of concentration In the RAC exposure group,the swimming speed increased firstly and then decreased with the increase of concentration.These adrenergic receptor related pharmaceuticals can affect the transcriptional level of genes involved in the nervous system,and the change of acetylcholine esterase enzyme activity was consistent with the change of its gene transcription level.Additionally,MOX exposure resulted in a decline for blood vessel diameter in zebrafish,and increased blood flow volume and heart rate.After PRO exposure,blood vessel diameter,blood flow volume and heart rate were decreased.RAC exposure significantly decreased the vascular diameter,while increased blood flow volume.The heart rates were increased firstly while decreased with the increase of concentration.The mRNA levels of key transcriptional regulators in cardiogenesis changed as well after exposure,which demonstrated that adrenergic receptor related pharmaceuticals can affect the development of the cardiovascular system.In conclusion,these adrenergic receptor related pharmaceuticals could affect the embryonic development,disrupt the development and function of nerve system and cardiovascular system,and led to the behavior toxicity,and the results will be helpful for filling the data gaps in toxicological profiles and consequently for a full ecotoxicological risk assessment of these chemicals.