Dataset Information

Chronic Effects of Carbamazepine, Progesterone and Their Mixtures at Environmentally Relevant Concentrations on Biochemical Markers of Zebrafish (Danio rerio).

ABSTRACT: The impact of pharmaceuticals on non-target organisms in the environment is of increasing concern and study. Pharmaceuticals and other pollutants are often present as mixtures in an environmental compartment. Studies on the toxicological implications of these drugs on fish, particularly as mixtures at environmentally relevant concentrations, are very limited. Thus, this study aimed to evaluate the chronic effects of the anticonvulsant drug carbamazepine (CBZ) and progesterone (P4) at environmentally relevant concentrations, individually and in binary mixtures, applying a suite of biomarkers at the molecular level in zebrafish (Danio rerio). The effects on biotransformation enzymes 7-ethoxyresorufin O-deethylase (EROD) and glutathione-S-transferase (GST), antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidases (GPxSe and GPxTOT), and glutathione reductase (GR), and markers of damage, such as DNA strand breaks (DNAsb), lactate dehydrogenase (LDH), lipid peroxidation (LPO), and vitellogenin-like proteins (VTG), were evaluated. Analyses of the biochemical markers indicated that a synergistic dose-ratio-dependent effect of CBZ and P4 in zebrafish occurs after chronic exposure regarding VTG, biotransformation enzymes (EROD, GST), and oxidative stress marker (DNAsb). The results suggest a synergistic effect regarding VTG, thus indicating a high risk to the reproductive success of fish if these pharmaceuticals co-occur.

SUBMITTER: Acs A

PROVIDER: S-EPMC9495832 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Chronic Effects of Carbamazepine, Progesterone and Their Mixtures at Environmentally Relevant Concentrations on Biochemical Markers of Zebrafish (<i>Danio rerio</i>).

Ács András A Liang Xinyue X Bock Illés I Griffitts Jeffrey J Ivánovics Bence B Vásárhelyi Erna E Ferincz Árpád Á Pirger Zsolt Z Urbányi Béla B Csenki Zsolt Z

Antioxidants (Basel, Switzerland) 20220908 9

The impact of pharmaceuticals on non-target organisms in the environment is of increasing concern and study. Pharmaceuticals and other pollutants are often present as mixtures in an environmental compartment. Studies on the toxicological implications of these drugs on fish, particularly as mixtures at environmentally relevant concentrations, are very limited. Thus, this study aimed to evaluate the chronic effects of the anticonvulsant drug carbamazepine (CBZ) and progesterone (P4) at environment ...[more]

PMID: 36139850

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Project description:Concerns regarding environmental exposures and the impacts of pharmaceuticals on non-target aquatic organisms continue to increase. The antiepileptic drug carbamazepine (CBZ) is often detected as an aquatic contaminant and can disrupt various behaviors of fishes. However, there are few reports which investigate the mechanism of CBZ action in fish. The aim of the current study was to evaluate the effects of CBZ on embryonic development (i.e., hatching rate, heart rate, and body length) and early spontaneous movement. Moreover, we sought to investigate potential mechanisms by focusing on the gamma-aminobutyric acid (GABA) neurotransmitter system in zebrafish 6 days after of exposure. The results show that CBZ exposure did not cause significant effects on embryo development (hatching rate, heart rate, nor body length) at the test concentrations. However, the early spontaneous movement of embryos was inhibited following 10 μg/L CBZ exposure at 28-29 h post-fertilization (hpf). In addition, acetylcholinesterase (AChE) activity and GABA concentrations were increased with exposure, whereas glutamate (Glu) concentrations were decreased in larval zebrafish. Gene expression analysis revealed that GABA and glutamate metabolic pathways in zebrafish larvae were altered following exposure to CBZ. GABA transaminase (abat) and glutamic acid decarboxylase (gad1b) decreased to 100 µg/L, and glutamate receptor, ionotropic, N-methyl D-aspartate 1b (grin1b) as well as the glutamate receptor, ionotropic, α-amino-3hydroxy-5methylisoxazole-4propionic 2b (gria2b) were down-regulated with exposure to 1 µg/L CBZ. Our study suggests that CBZ, which can act as an agonist of the GABAA receptor in humans, can also induce alterations in the GABAergic system in fish. Overall, this study improves understanding of the neurotoxicity and behavioral toxicity of zebrafish exposed to CBZ and generates data to be used to understand mechanisms of action that may underlie antiepileptic drug exposures.

Project description:ObjectiveThis study was aimed to explore the role of AhR in the neurotoxicity of adult zebrafish induced by three typical bisphenol compounds (BPA, BPS, TBBPA) at environmentally relevant doses.MethodsThe adult zebrafish were randomly divided into solvent control group (DMSO) and AhR inhibitor CH223191 (CH) group (0.05 μmol/L), bisphenol exposure groups (10, 100, 1000 nmol/L) and combined exposure groups (0.05 μmol/L CH and 1000 nmol/L bisphenol compounds). Each tank contained 8 fish (4 male and 4 female), and two parallel tanks were set synchronously. After 30 days of exposure, zebrafish were put on ice plate for anesthesia, weighed and measured for body length, and dissected for brain tissue. The gene expression was detected by RT-qPCR, and the activities of antioxidant enzymes were detected by commercial kits. SPSS 26.0 was used to analyze the data. Additionally, GO, KEGG and principal component analysis (PCA) were carried out.ResultsCompared with the solvent control group, there were no significant differences in body weight and length among the exposed groups. In general, exposure to bisphenol compounds could affect the expression of Ahr2 and AhR target genes (cyp1a1, cyp1a2, and cyp1c1), key genes of neural function (elavl3, gfap, mbp, syn2a, gap43, Zn5, shha, and ache), oxidative stress related genes (nrf2, gpx1a, gstp1/gstp1.2, gstp2/gstp1.1, sod1, sod2, and cat), and the activities of antioxidant enzymes (SOD, CAT and GSH-Px/GPX) in zebrafish brain tissue to some extent. Compared with the groups exposed to bisphenols alone, CH could antagonize the above interference effects caused by bisphenols to some extent. Therefore, the toxic effects of BPA, BPS and TBBPA might be produced through similar mechanisms.ConclusionEnvironmentally related doses of bisphenols (BPA, BPS, TBBPA) could disturb the expression of key molecules of oxidative stress and neural function through activating the AhR signaling pathway, and ultimately lead to neurotoxicity.

Dataset Information

Chronic Effects of Carbamazepine, Progesterone and Their Mixtures at Environmentally Relevant Concentrations on Biochemical Markers of Zebrafish (Danio rerio).

Publications

Chronic Effects of Carbamazepine, Progesterone and Their Mixtures at Environmentally Relevant Concentrations on Biochemical Markers of Zebrafish (<i>Danio rerio</i>).

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