State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products / Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang Province, Institute of Quality and Standard of Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China; Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, College of Agriculture and Food Science, Zhejiang A & F University, Lin'an, Zhejiang, 311300, PR China.
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products / Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang Province, Institute of Quality and Standard of Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China; Collaborative Innovation Center of Green Pesticide, Zhejiang A & F University, Lin'an, 311300, Zhejiang Province, China.
Environ Pollut. 2021 Feb 1;270:116182. doi: 10.1016/j.envpol.2020.116182. Epub 2020 Dec 5.
Fluoxetine is frequently detected in aquatic environment, and chronic FLX exposure exhibits adverse effects on aquatic communities. Its chirality makes the adverse effects more complicated. This study aimed at the enantioselective cardiotoxicity in developmental zebrafish induced by racemic (rac-)/S-/R-fluoxetine. The accumulation profiles demonstrated that biotransformation of fluoxetine to norfluoxetine occurred during rac-fluoxetine exposure, with a higher enrichment of S-norfluoxetine than R-norfluoxetine. Heart malformations including pericardial edema, circulation abnormalities, and thrombosis were observed, and enantioselective changes also occurred. According to H&E staining and Masson's trichrome staining, the loose severity of cardiac structure and cardiac fibrosis in rac-norfluoxetine treated group was worse than that in fluoxetine treated groups. Results of toxicity-associated parameters in our homochiral enantiomers' exposure also indicated that the toxicity induced by S-fluoxetine was more severe than R-fluoxetine. Enantioselective arrhythmia in developmental zebrafish after chiral fluoxetine exposure could be caused by myocardial fibrosis, abnormal developmental processes, and the biotransformation of fluoxetine to norfluoxetine could make that worse. Our findings can be used to assess the environmental risk of the two enantiomers of fluoxetine that induce cardiotoxicity in aquatic organisms.
氟西汀经常在水生环境中被检测到，慢性 FLX 暴露对水生群落表现出不良影响。其手性使不良影响更加复杂。本研究旨在研究外消旋（rac-）/S-/R-氟西汀对发育中的斑马鱼的心脏选择性毒性。积累谱表明，氟西汀在暴露于外消旋氟西汀期间发生了向 norfluoxetine 的生物转化，S-norfluoxetine 的富集度高于 R-norfluoxetine。观察到心脏畸形，包括心包水肿、循环异常和血栓形成，并且发生了对映体选择性变化。根据 H&E 染色和 Masson 三色染色，rac-norfluoxetine 处理组的心脏结构疏松程度和心脏纤维化比氟西汀处理组更严重。我们在同手性对映异构体暴露中的毒性相关参数的结果也表明，S-氟西汀引起的毒性比 R-氟西汀更严重。手性氟西汀暴露后发育中的斑马鱼的对映选择性心律失常可能是由心肌纤维化、异常发育过程以及氟西汀向 norfluoxetine 的生物转化引起的。我们的研究结果可用于评估氟西汀两种对映体在水生生物中引起心脏毒性的环境风险。
