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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ibuprofen (IBU), as a commonly used non-steroidal anti-inflammatory drug (NSAID) and pharmaceutical and personal care product (PPCP), is frequently prescribed by doctors to relieve pain. It is widely released into environmental water and soil in the form of chiral enantiomers by the urination and defecation of humans or animals and by sewage discharge from wastewater treatment plants. This study focused on the alteration of metabolism in the adult zebrafish (Danio rerio) brain after exposure to R-(-)-/S-(+)-/rac-IBU at 5 μg L -1 for 28 days. A total of 45 potential biomarkers and related pathways, including amino acids and their derivatives, purine and its derivatives, nucleotides and other metabolites, were observed with untargeted metabolomics. To validate the metabolic disorders induced by IBU, 22 amino acids and 3 antioxidant enzymes were selected to be quantitated and determined using targeted metabolomics and enzyme assay. Stereoselective changes were observed in the 45 identified biomarkers from the untargeted metabolomics analysis. The 22 amino acids quantitated in targeted metabolomics and 3 antioxidant enzymes determined in enzyme assay also showed stereoselective changes after R-(-)-/S-(+)-/rac-IBU exposure. Results showed that even at a low concentration of R-(-)-/S-(+)-/rac-IBU, disorders in metabolism and antioxidant defense systems were still induced with stereoselectivity. Our study may enable a better understanding of the risks of chiral PPCPs in aquatic organisms in the environment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the oxidative stress process and bioaccumulation the racemic/(-)-/(+)- 2,2',3,4',6-pentachlorobiphenyl were administered to adult zebrafish (Danio rerio) after prolonged exposure of 56-days uptake and 49-days depuration experiments. Stereoselective accumulation was observed in adult samples after racemic exposure as revealed by decreased enantiomer fractions. The two enantiomers of PCB91 accumulated at different rates with logBCFk values close to 3.7, suggesting that they were highly hazardous and persistent pollutants. Exposure to racemic/(-)-/(+)- PCB91 stereoselectively induced oxidative stress owing to changes in reactive oxygen species, malondialdehyde contents, antioxidant enzyme activities and gene expressions in brain and liver tissues. In addition, the stereoselective relationship between bioconcentration and oxidative stress were also presented in this study. Our findings might be helpful for elucidating the environmental risk of the two enantiomers of PCB91 that induce toxicity in aquatic organisms., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Difenoconazole is a widely used triazole fungicide and has been reported to have negative impacts on zebrafish embryos. To investigate the mechanism of its developmental toxicity, zebrafish embryos were exposed to 0.5 and 2.0 mg/L difenoconazole for 96 h. The morphological and physiological indicators of embryo development were tested. The total cholesterol (TCHO) level, triglyceride (TG) level and malondialdehyde (MDA) content were measured at 96 hpf (hours post-fertilization). In addition, the transcription of genes related to embryo development, the antioxidant system, lipid synthesis and metabolism was quantified. Our results showed that a large suite of symptoms were induced by difenoconazole, including hatching regression, heart rate decrease, growth inhibition and teratogenic effects. 0.5 mg/L difenoconazole could significantly increase the TG content of zebrafish embryos at 96 hpf, while no apparent change in the TCHO and MDA level was observed post 96 h exposure. Q-PCR (quantitative real-time polymerase chain reaction) results showed that the transcription of genes related to embryonic development was decreased after exposure. Genes related to hatching, retinoic acid metabolism and lipid homeostasis were up-regulated by difenoconazole., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cyhalofop-butyl is a selective herbicide widely employed in paddy field, which can transfer into aquatic environments. However, details of the environmental risk and aquatic toxicity of cyhalofop-butyl have not been fully investigated. In this study, zebrafish (Danio rerio) embryos were exposed to a range of cyhalofop-butyl until 120 hour post-fertilization (hpf) to assess embryonic toxicity of the chemical. Our results demonstrated that cyhalofop-butyl was highly toxic to zebrafish embryos, with concentration-dependent negative effects in embryonic development. In addition, exposure to cyhalofop-butyl resulted in significant increases in reactive oxygen species (ROS) production and cell apoptosis in heart area. The mRNA levels of the genes related to oxidative stress and apoptosis were also altered significantly after cyhalofop-butyl exposure. Moreover, the activity of capspase-9 and caspase-3 were significantly increased. Therefore, we speculated that oxidative stress-induced apoptosis should be responsible for abnormal development during embryogenesis after cyhalofop-butyl exposure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Difenoconazole is a widely used triazole fungicide, its extensive application may potentially cause toxic effects on non-target organisms. To investigate the effect of difenoconazole on cholesterol content and related mechanism, adult zebrafish were exposed to environmental related dosage (0.1, 10 and 500 μg/L) difenoconazole. The body weight and hepatic total cholesterol (TCHO) level was tested at 7, 15 and 30 days post exposure (dpe). The expressions of eight cholesterol synthesis genes and one cholesterol metabolism gene were assessed via Quantitative PCR method. The significant decrease of TCHO level in male zebrafish liver was observed at 15 and 30 dpe, which was accompanied by apparent hepatic cholesterol-genesis genes expression decline. In comparison with males, female zebrafish showed different transcription modification of tested genes, and the cholesterol content maintain normal level during the whole exposure., (Copyright © 2014 Elsevier Ltd. All rights reserved.)