| Adrenergic receptor related pharmaceuticals are considered as one class of emerging environmental contaminants in the aquatic environment.Because adrenergic receptor drugs are widely detected in the aquatic environment and are biologically active,their ecotoxicological effects on non-target organisms(particularly fish)must be of concern.In order to explore their toxic effectives on teleost,the toxic effectives of ?-blocker propranolol,?-blocker moxisylyte and ?-adrenergic receptor agonist ractopamine were assessed on medaka larvae or adult in this study.Firstly,we determined the effects of ?-blocker propranolol and its enantiomers on physiological indicators and transcriptional responses of genes involved in the various physiological processes,including antioxidant,detoxification and endocrine system,as well as hepatic activities of antioxidant enzymes,in medaka larvae following exposure for 28 or 44 days.The results showed that propranolol and its enantiomers resulted in the decrease of hatchling rate,the total survival rate,body length and weight.In addition,enantioselective differences of toxic effects were found.The transcript levels of the detoxificationan genes Cytochrome P450 1A1(CYP1A1)and Cytochrome P450 3A(CYP3A)were significantly increased.The transcript levels of the antioxidant genes Superoxide dismutase(SOD),Catalase(CAT),Glutathione S-transferase(GST),Glutathione peroxidase(GPX),as well as hepatic activities of antioxidant enzymes,were significantly increased as well.We also found that propranolol and its enantiomers significantly changed the expression profiles of a set of genes involved in the hypothalamic-pituitary-gonadal(HPG)axis.The transcript levels of Vitellogenin(VTG),Eetrogen receptor a(ER?)and Eetrogen receptor?(ER[?)were significantly decreased.Moreover,it was observed more toxic effects on medaka larvae exposed for 28 days than that exposed for 44 days.The results obtained in the present study indicated that the exposure to propranolol and its enantiomers can induce oxidative stress and endocrine disruption in madake larvae with obvious enantioselective effects.Secondly,we studied the changes in the expression of oxidative stress,detoxification and endocrine system related genes in the medaka larvae following exposure to moxisylyte for 28 or 44 days.In addition,the morphology of tissue and the transcriptional responses of genes in liver,gonads and brain tissue were also determined in adult of medaka.The results indicated that 625 ?g/L moxisylyte resulted in the decrease of the hatchling rate,the total survival rate,body length and weight of male medaka.The transcript levels of the antioxidant genes SOD and GST,as well as hepatic activities of antioxidant enzymes,were significantly increased in male medaka exposed to moxisylyte for 44 days.Moreover,the exposure with moxisylyte significantly reduced the transcript levels of a set of genes involved in the HPG axis,and it induced more toxic effects in the males than that in females.Furthermore,the morphology of liver tissue changed after the exposure with moxisylyte.The results showed that moxisylyte caused great impacts on the HPG axis with obvious gender-or tissue-specific effects.Finally,we evaluated the effects of ractopamine on medaka larvae.Ractopamine reduced the transcript levels of GST and GPX,while it upregulated the transcript levels of Glutathione reductase(GR).Ractopamine affected the transcript levels of endocrine-related genes.The transcript levels of VTG and steroid hormone synthesis related genes,such as Cytochrome P450 11A(CYP11A)and Cytochrome P45017(CYP17),were significantly upregulated in female medaka,which displayed specific effects with obvious gender-difference.In conclusion,propranolol,moxisylyte and ractopamine could affect medaka on physiological and gene level.The results obtained in this study will be helpful for improving the risk assessment for these pharmaceuticals. |
PDF Full Text Request