The antidepressant drug Carbamazepine induces differential transcriptome expression in the brain of Atlantic salmon, Salmo salar

Hampel, Miriam; Bron, James E.; Taggart, John B.; Leaver, Michael J.

doi:10.1016/j.aquatox.2013.12.018

Cited by 37 publications

(8 citation statements)

References 82 publications

(78 reference statements)

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“…Environmentally relevant concentrations of CBZ have been shown to affect fish more often during chronic exposures compared to acute exposures [14,36,37]. Acute toxicity tests have revealed that CBZ is unlikely to be lethal at environmental levels, with reported LC50 (median lethal concentration) and EC50 (median effective concentration) values approaching mg/L levels, and do not exert effects on major physiological processes, such as growth and activity [37]. For example, the 96 h LC50 values for CBZ in O. latipes is 35.4 mg/L [36], which is much higher than reported levels in the environment.…”

Section: Discussionmentioning

confidence: 99%

Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio)

Chen

Yang

Zhao

et al. 2020

IJERPH

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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.

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Section: Discussionmentioning

confidence: 99%

Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio)

Chen

Yang

Zhao

et al. 2020

IJERPH

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“…priority lists because of their persistence and potential health risks (Costanzo et al, 2007;Hampel et al, 2014).…”

Section: Detections Of Pharmaceuticals In Dwssmentioning

confidence: 99%

Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China

Sun

Luo

Wang

et al. 2015

Ecotoxicology and Environmental Safety

132

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a b s t r a c tPharmaceuticals in drinking water sources (DWSs) have raised significant concerns for their persistent input and potential human health risks. Currently, little is known about the occurrence of pharmaceuticals in DWSs in China. In this study, a survey for multi-class pharmaceuticals in DWSs of five major river watersheds in China was conducted from 2012 to 2013. Samples were collected from 25 sampling sites in rivers and reservoirs. 135 pharmaceuticals were analyzed using solid-phase extraction and ultra-performance liquid chromatography tandem mass spectrometry. The results showed that a total of 70 pharmaceuticals were present in the samples, and the most frequently detected ones included sulfonamides, macrolides, antiepileptic drugs, anti-inflammatory drugs, and β-blockers, etc. Amongst these, maximum concentrations of lincomycin, sulfamethoxazole, acetaminophen and paraxanthine were between 44 ng/L and 134 ng/L, and those of metoprolol, diphenhydramine, venlafaxine, nalidixic acid and androstenedione were less than 1 ng/L. Concentrations of the two that were most persistent, DEET and carbamazepine, were 0.8-10.2 ng/L and 0.01-3.5 ng/L, respectively. Higher concentrations of cotinine were observed in warm season than in cold season, while concentrations of lincomycin were the opposite. In a causality analysis, the occurrence of pharmaceuticals in DWSs depends mainly on the detection limits of the methods, their usage and the persistence in the aquatic environment.

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“…GPCRs mediate most of vertebrate physiological responses to hormones and neurotransmitters (Rosenbaum et al, 2009). They are also the targets for a large number of pollutants and toxicants that could disrupt neuroendocrine system in fish such as MeHg, carbamazepine (Hampel et al, 2014). In our study, a decrease of GNAO and GNAI2 was observed in response to BT.…”

Section: Discussionmentioning

confidence: 51%

Brain quantitative proteomic responses reveal new insight of benzotriazole neurotoxicity in female Chinese rare minnow (Gobiocypris rarus)

et al. 2016

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a b s t r a c tBenzotriazole (BT) is a high-production volume chemical which has been ubiquitously detected in aquatic environments. Although adverse effects from acute and chronic exposure to BT have been reported, the neurotoxic effect of BT and the mechanisms of toxicity are not well documented. In this study, adult female Chinese rare minnow (Gobiocypris rarus) were exposed to 0.05, 0.5, and 5 mg/L BT for 28 days. The brain proteome showed that BT exposure mainly involved in metabolic process, signal transduction, stress response, cytoskeleton, and transport. Pathway analysis revealed that cellular processes affected by BT included cellular respiration, G-protein signal cascades, Ca 2+ -dependent signaling, cell cycle and apoptosis. Moreover, data on relative mRNA levels demonstrated that genes related to these toxic pathways were also significantly affected by BT. Furthermore, proteins affected by BT such as CKBB, GS, HPCA, VDAC1, and FLOT1A are associated with neurological disorders. Therefore, our finding suggested that BT induced molecular responses in the brain and could provide new insight into BT neurotoxicity in Chinese rare minnow.

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The antidepressant drug Carbamazepine induces differential transcriptome expression in the brain of Atlantic salmon, Salmo salar

Cited by 37 publications

References 82 publications

Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio)

Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio)

Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China

Brain quantitative proteomic responses reveal new insight of benzotriazole neurotoxicity in female Chinese rare minnow (Gobiocypris rarus)

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