Behavioral profile alterations in zebrafish larvae exposed to environmentally relevant concentrations of eight priority pharmaceuticals

Lu, Peili; Chen, Qiqing; Paolo, Carolina Di; Shao, Ying; Hollert, Henner; Seiler, Thomas‐Benjamin

doi:10.1016/j.scitotenv.2019.01.300

Cited by 49 publications

(22 citation statements)

References 57 publications

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“…Growth retardation was observed with a significant delay in hatching at 48 hpf and 72 hpf for 250 µM PHE but for CBZ it was only observable at 72 hpf. Those results are also in accordance with other studies for PHE [51,52], but no developmental delays were reported yet for CBZ, to our knowledge. However, differences for some morphological endpoints were also observed from the investigation of Weigt et al [35].…”

Section: Discussionsupporting

confidence: 94%

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

Bars

Hoyberghs

Valenzuela

et al. 2021

IJMS

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The zebrafish (Danio rerio) embryo is gaining interest as a bridging tool between in-vitro and in-vivo developmental toxicity studies. However, cytochrome P450 (CYP)-mediated drug metabolism in this model is still under debate. Therefore, we investigated the potential of zebrafish embryos and larvae to bioactivate two known anti-epileptics, carbamazepine (CBZ) and phenytoin (PHE), to carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. First, zebrafish were exposed to CBZ, PHE, E-CBZ and HPPH from 5¼- to 120-h post fertilization (hpf) and morphologically evaluated. Second, the formations of E-CBZ and HPPH were assessed in culture medium and in whole-embryo extracts at different time points by targeted LC-MS. Finally, E-CBZ and HPPH formation was also assessed in adult zebrafish liver microsomes and compared with those of human, rat, and rabbit. The present study showed teratogenic effects for CBZ and PHE, but not for E-CBZ and HPPH. No HPPH was detected during organogenesis and E-CBZ was only formed at the end of organogenesis. E-CBZ and HPPH formation was also very low-to-negligible in adult zebrafish compared with the mammalian species. As such, other metabolic pathways than those of mammals are involved in the bioactivation of CBZ and PHE, or, these anti-epileptics are teratogens and do not require bioactivation in the zebrafish.

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Section: Discussionsupporting

confidence: 94%

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

Bars

Hoyberghs

Valenzuela

et al. 2021

IJMS

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“…Behavioral studies may give some clues about pollutants' impacts on organisms. The light-dark transition test is appropriate as it induces stress evaluated by the distance moved by the larvae, a measurable parameter to assess toxic substances impacts [41,63]. Thus, locomotor activity following alternating light-dark photostimulation was analyzed for 6 dpf-old zebrafish larvae exposed to RR samples (Figure 1).…”

Section: Light-dark Stress Testmentioning

confidence: 99%

Road Runoff Characterization: Ecotoxicological Assessment Combined with (Non-)Target Screenings of Micropollutants for the Identification of Relevant Toxicants in the Dissolved Phase

Sandré

Huynh

Gromaire

et al. 2022

Water

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Road runoff (RR) is an important vector of micropollutants towards groundwater and soils, threatening the environment and ecosystems. Through combined chemical and biological approaches, the purpose of this study was to get insights on specific toxicants present in RR from two sites differing by their traffic intensity and their toxicological risk assessment. Non-target screening was performed by HRMS on RR dissolved phase. Ecotoxicological risk was evaluated in a zebrafish embryos model and on rat liver mitochondrial respiratory chain. Specific HRMS fingerprints were obtained for each site, reflecting their respective traffic intensities. Several micropollutants, including 1,3-diphenylguanidine (DPG) and benzotriazole (BZT) were identified in greater concentrations at the high-traffic site. The origin of DPG was confirmed by analyzing HRMS fingerprints from shredded tires. RR samples from each site, DPG and BZT were of relatively low toxicity (no mortality) to zebrafish embryos, but all generated distinct and marked stress responses in the light–dark transition test, while DPG/BZT mixes abolished this effect. The moderate-traffic RR and DPG inhibited mitochondrial complex I. Our study highlights (i) the unpredictability of pollutants cocktail effect and (ii) the importance of a multi-approaches strategy to characterize environmental matrices, essential for their management at the source and optimization of depollution devices.

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“…Antibiotics’ negative impacts on aquatic organisms were reported, including effects on survival, growth, reproductive ability, and biochemical markers alterations; hence, antibiotics affect the entire food chain of aquatic organisms. However, the consequences of antibiotic exposure on aquatic animal behavior have rarely been studied [ 3 , 20 ]. The use of behavioral changes to evaluate the sublethal effects of chemicals on non-target aquatic creatures is becoming increasingly popular [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Locomotion Complexity in Zebrafish after Exposure to Twenty Antibiotics by Fractal Dimension and Entropy Analysis

et al. 2022

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Antibiotics are extensively used in aquaculture to prevent bacterial infection and the spread of diseases. Some antibiotics have a relatively longer half-life in water and may induce some adverse effects on the targeted fish species. This study analyzed the potential adverse effects of antibiotics in zebrafish at the behavioral level by a phenomic approach. We conducted three-dimensional (3D) locomotion tracking for adult zebrafish after acute exposure to twenty different antibiotics at a concentration of 100 ppb for 10 days. Their locomotor complexity was analyzed and compared by fractal dimension and permutation entropy analysis. The dimensionality reduction method was performed by combining the data gathered from behavioral endpoints alteration. Principal component and hierarchical analysis conclude that three antibiotics: amoxicillin, trimethoprim, and tylosin, displayed unique characteristics. The effects of these three antibiotics at lower concentrations (1 and 10 ppb) were observed in a follow-up study. Based on the results, these antibiotics can trigger several behavioral alterations in adult zebrafish, even in low doses. Significant changes in locomotor behavioral activity, such as total distance activity, average speed, rapid movement time, angular velocity, time in top/bottom duration, and meandering movement are highly related to neurological motor impairments, anxiety levels, and stress responses were observed. This study provides evidence based on an in vivo experiment to support the idea that the usage of some antibiotics should be carefully addressed since they can induce a significant effect of behavioral alterations in fish.

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Behavioral profile alterations in zebrafish larvae exposed to environmentally relevant concentrations of eight priority pharmaceuticals

Cited by 49 publications

References 57 publications

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

Developmental Toxicity and Biotransformation of Two Anti-Epileptics in Zebrafish Embryos and Early Larvae

Road Runoff Characterization: Ecotoxicological Assessment Combined with (Non-)Target Screenings of Micropollutants for the Identification of Relevant Toxicants in the Dissolved Phase

Evaluation of Locomotion Complexity in Zebrafish after Exposure to Twenty Antibiotics by Fractal Dimension and Entropy Analysis

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