Search

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.)

The stereoselective effects of chiral ibuprofen (IBU) were studied using lipidomics by exposing adult zebrafish (Danio rerio) to an environmental concentration of 5 μg/L for 28 days. After treatment with rac-/R-(-)-/S-(+)-IBU, the brain tissue of the zebrafish was harvested to analyze for lipid metabolites by using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results showed that the six classes of lipids, namely, glycerophospholipids, sterol lipids, prenol lipids, fatty acyls, glycerolipids, and sphingolipids, including 46 biomarkers, were affected after exposure. The different influences on metabolites were observed in the rac-/R-(-)-/S-(+)-IBU-treated samples. The rac-IBU treatment remarkably affected nine lipids. The R-(-)-IBU and S-(+)-IBU treatments had remarkably effects on six and four lipids, respectively. According to the HMDB database and KEGG pathways, nine important lipids were successfully matched to the involved biochemical pathways, such as glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. Therefore, IBU can cause disorders in the metabolism of the brain lipids of adult zebrafish and affect the composition of biological membranes, inflammatory responses, and cardiovascular and cerebrovascular diseases. The significant difference in the effects of R-(-)-IBU and S-(+)-IBU on lipidomics indicated that chiral IBU has stereoselective toxicity to aquatic organisms. Our study provided new insights into the environmental toxicology and highlighted the hazard of pharmaceutical and personal care product pollution in aquatic environments., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. 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.)

In this study, we aimed to investigate the dysfunction of zebrafish embryos and larvae induced by rac-/(+)-/(-)- PCB91 and rac-/(-)-/(+)- PCB149. UPLC-MS/MS (Ultra-performance liquid chromatography coupled with mass spectrometry) was employed to perform targeted metabolomics analysis, including the quantification of 22 amino acids and the semi-quantitation of 22 other metabolites. Stereoselective changes in target metabolites were observed in embryos and larvae after exposure to chiral PCB91 and PCB149, respectively. In addition, statistical analyses, including PCA and PLS-DA, combined with targeted metabolomics were conducted to identify the characteristic metabolites and the affected pathways. Most of the unique metabolites in embryos and larvae after PCB91/149 exposure were amino acids, and the affected pathways for zebrafish in the developmental stage were metabolic pathways. The stereoselective effects of PCB91/149 on the metabolic pathways of zebrafish embryos and larvae suggest that chiral PCB91/149 exposure has stereoselective toxicity on the developmental stages of zebrafish.

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.)

This paper was designed to study stereoselective enrichment and changes in gene expression when zebrafish (Danio rerio) embryo-larvae were exposed to racemic, (-)- or (+)- PCB149 (2,2',3,4',5',6- hexachlorobiphenyl). Based on bioconcentration analysis, non-racemic enrichment was significantly observed after racemic exposure. No isomerization between the two isomers was found after (-)/(+)-PCB149 exposure. Furthermore, based on gene expression-data mining, CYPs genes (cyp2k6, cyp19a1b, and cyp2aa4) were differential genes after (+)-PCB149 exposure. No obvious differences of dysregulation of gene expression caused by racemic and (-)-PCB149, were observed in embryo-larvae. The above results suggested that (-)-PCB149 could be considered as the main factor causing the dysregulation of gene expression in embryo-larvae after racemic exposure; and (+)-PCB149 should be pursued apart from the racemate, when considering the toxicity of chiral PCB149. Thus, the information in our study could provide new insights to assess the environmental risk of chiral PCBs in aquatic systems.

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.)

Enantioselective enrichment of chiral PCB149 (2,2',3,4',5',6-hexachlorobiphenyl) was analysed in adult zebrafish (Danio rerio) exposed to the racemate, (-)-PCB149, and (+)-PCB149. Greater enrichment of (-)-PCB149 compared to (+) PCB149 was observed following 0.5 ng/L exposure; however, as the exposure time and concentration increased, racemic enrichment was observed in adult fish exposed to the racemate. No biotransformation between the two isomers was observed in fish exposed to single enantiomers. When zebrafish were exposed to different forms of chiral PCB149, enantioselective expression of genes associated with polychlorinated biphenyls (PCBs) was observed in brain and liver tissues and enantioselective correlations between bioconcentration and target gene expression levels were observed in brain and liver tissues. The strong positive correlations between expression levels of target genes (alox5a and alox12) and PCB149 bioconcentration suggest that prolonged exposure to the racemate of chiral PCB149 may result in inflammation-associated diseases. Prolonged exposure to (-)-PCB149 may also affect metabolic pathways such as dehydrogenation and methylation in the brain tissues of adult zebrafish. Hepatic expression levels of genes related to the antioxidant system were significantly negatively correlated with bioconcentration following exposure to (+)-PCB149.

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.)

We report here an investigation of the mechanisms contributing to the divergent sensitivity toward the triazole fungicide difenoconazole of zebrafish (Danio reio) during different life stages. Adult and embryonic zebrafish were exposed to three different concentrations of difenoconazole (0.01, 0.5 and 1.0mg/L). The death rate, bioaccumulation of difenoconazole, oxidative stress parameters and transcription of related genes were tested at 4 and 8 days post-exposure (dpe). The death rate for adult zebrafish was much higher than that of the embryos at an exposure concentration of 1.0mg/L at both 4 and 8 dpe. The concentrations of difenoconazole in both the embryos and adult fish were similar, except for the group exposed to 0.01mg/L difenoconazole. A decrease in antioxidant enzyme activities was observed in both the embryos and the livers of adult fish after exposure to difenoconazole. Significant lipid peroxidation was found in the livers of adult fish in all exposure groups at 8 dpe, but was not observed in the treated embryos. The gene transcription response of the embryos toward difenoconazole was different from that in the livers of adult fish at 4 dpe. At 8 dpe, the modification in the transcription of the tested genes in the embryos and adult fish was similar, except for the genes related to the synthesis of sterols., (Copyright © 2015 Elsevier B.V. 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.)

Mefentrifluconazole is a new chiral triazole fungicide with high efficiency and broad spectrum. Zebrafish embryos, larvae and adults were exposed to mefentrifluconazole racemate and enantiomers to investigate aquatic toxicity of mefentrifluconazole at the enantiomer level. Acute toxicity tests were conducted to determine the lethality of mefentrifluconazole. The developmental toxicity of mefentrifluconazole to embryos and larvae was also assessed during acute exposure. Besides, the growth parameters of adults were evaluated after 14 days' exposure. The 96-h LC 50 ranges of rac-, R-(−)- and S-(+)-mefentrifluconazole to all zebrafish life-stages were 0.753–1.198, 1.092–2.022 and 0.583–1.056 mg/L respectively. Larvae were the most sensitive to mefentrifluconazole in terms of lethality, followed by embryos and adults. During acute exposure, morphological deformities caused by mefentrifluconazole, such as yolk sac edema and pericardial edema in embryos, as well as pericardial edema and spinal curvature in larvae were discovered. Besides, mefentrifluconazole induced significant developmental defects, including inhibited heartbeat and reduced body length in both embryos and larvae. After 14 days' mefentrifluconazole exposure, severe growth inhibition in adult zebrafish was observed. Mefentrifluconazole shows enantioselective toxicity in all stages of zebrafish, and the order of toxicity is S-(+)-mefentrifluconazole > rac-mefentrifluconazole > R-(−)-mefentrifluconazole. Further study is required to explore the specific enantioselective mechanism. Our findings enable a better understanding of the potential risk of mefentrifluconazole to aquatic ecosystems at the enantiomer level. [Display omitted] • Mefentrifluconazole showed strong lethality to zebrafish. • Mefentrifluconazole induced severe developmental effects on multiple stages of zebrafish. • S-(+)-mefentrifluconazole exerted higher toxicity to zebrafish than R-(−)-mefentrifluconazole. [ABSTRACT FROM AUTHOR]