Study on early biomarkers of zebrafish liver injury induced by acetaminophen

Guo, Qiuping; Yang, Wei; Xiao, Baiquan; Zhang, Hong; Lei, Xialing; Ou, Huiyu; Qin, Renan; Ruo-min, Jin

doi:10.3109/15569543.2014.986282

Cited by 11 publications

(5 citation statements)

References 43 publications

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“…It is, therefore, proposed that cellular damage to hepatocytes, associated with AFB1 exposure, leads to loss of context-specific glutaminase and transaminase activity and, consequently, impaired amino acid catabolism (and homeostasis, more generally), which contributes to toxicity in zebrafish embryos. This notion is supported, for example, by previous studies of the hepatotoxicity of acetaminophen in the zebrafish embryo, whereby a similar stage- and concentration-dependent embryotoxicity is correlated with the elevation of serum levels, and consequent loss in hepatocytes, of transaminase activity [42].…”

Section: Discussionmentioning

confidence: 67%

NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity

Zuberi

Eeza

Matysik

et al. 2019

Toxins

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Aflatoxin B1 (AFB1) is a widespread contaminant of grains and other agricultural crops and is globally associated with both acute toxicity and carcinogenicity. In the present study, we utilized nuclear magnetic resonance (NMR), and specifically high-resolution magic angle spin (HRMAS) NMR, coupled to the zebrafish (Danio rerio) embryo toxicological model, to characterize metabolic profiles associated with exposure to AFB1. Exposure to AFB1 was associated with dose-dependent acute toxicity (i.e., lethality) and developmental deformities at micromolar (≤ 2 µM) concentrations. Toxicity of AFB1 was stage-dependent and specifically consistent, in this regard, with a role of the liver and phase I enzyme (i.e., cytochrome P450) bioactivation. Metabolic profiles of intact zebrafish embryos exposed to AFB1 were, furthermore, largely consistent with hepatotoxicity previously reported in mammalian systems including metabolites associated with cytotoxicity (i.e., loss of cellular membrane integrity), glutathione-based detoxification, and multiple pathways associated with the liver including amino acid, lipid, and carbohydrate (i.e., energy) metabolism. Taken together, these metabolic alterations enabled the proposal of an integrated model of the hepatotoxicity of AFB1 in the zebrafish embryo system. Interestingly, changes in amino acid neurotransmitters (i.e., Gly, Glu, and GABA), as a key modulator of neural development, supports a role in recently-reported neurobehavioral and neurodevelopmental effects of AFB1 in the zebrafish embryo model. The present study reinforces not only toxicological pathways of AFB1 (i.e., hepatotoxicity, neurotoxicity), but also multiple metabolites as potential biomarkers of exposure and toxicity. More generally, this underscores the capacity of NMR-based approaches, when coupled to animal models, as a powerful toxicometabolomics tool.

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Section: Discussionmentioning

confidence: 67%

NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity

Zuberi

Eeza

Matysik

et al. 2019

Toxins

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“…Besides, XOD generated a large amount of ROS in the process of catalyzing hypoxanthine and xanthine to produce uric acid, which caused severe oxidative stressinduced hepatotoxicity. 54,55 The evidences have demonstrated that inflammation was closely related with the XOD and disorders of PUFA. 56,57 Excitingly, AAEO could reverse the disturbance of purine metabolism by reducing the activity of XOD, and significantly reduce oxidative stress and the inflammatory responses in liver tissues by increasing the mRNA expressions of SOD and CAT in mice liver tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The results indicated that AAEO treatment could reverse the disturbance of purine metabolism and reduce the production of UA by inhibiting the activity of XOD. Besides, XOD generated a large amount of ROS in the process of catalyzing hypoxanthine and xanthine to produce uric acid, which caused severe oxidative stress‐induced hepatotoxicity 54,55 . The evidences have demonstrated that inflammation was closely related with the XOD and disorders of PUFA 56,57 .…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

Cui

Zhou

Zhang

et al. 2023

Environmental Toxicology

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The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography–mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up‐regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA‐induced hepatotoxicity by reversing the occurrence of ferroptosis.

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“…APAP is a commonly used drug known for its analgesic and antipyretic effects and accepted as the model drug for dose-dependent, direct DILI studies (Klotz, 2012;Vliegenthart et al, 2014). While several studies employed zebrafish embryos and early larvae younger than 5 dpf showed that APAP induces hepatotoxicity in the zebrafish model, none of the previous studies tested larvae with fully functional liver (Guo et al, 2015;North et al, 2010;X. Zhang et al, 2014).…”

Section: Acetaminophen-induced Liver Size Reduction Only At 2-5 Dpf S...mentioning

confidence: 99%

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

Çakan Akdoğan,

Bilgi

2024

Biotech Studies

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Prediction of drug-induced liver injury (DILI) potential of drugs is one of the most challenging issues of drug development. Zebrafish larvae provide an in vivo and robust test platform. Due to the ease of handling developing larvae between 2 - 5 days post fertilization (dpf) has been extensively used as a DILI test model. However, the liver is not fully functional at this stage. Here, the importance of larval liver maturation was tested by applying selected known DILI-rank drugs to liver reporter zebrafish between 2-5 dpf and 5-7 dpf. Acetaminophen (most-DILI) treatment caused a significant dose-dependent reduction in liver size only at the early stage. Isoniazid (most-DILI) administration after liver maturation induced hepatomegaly, while it induced liver size reduction between 2-5 dpf. Chlorambucil (less-DILI) treatment induced opposing effects on liver size, in the two stages tested. A non-DILI agent chloramphenicol did not induce any liver size change in either larval stage. Clinical observations were better reproduced when isoniazid and chlorambucil were administered after liver maturation. Our findings show that often-overlooked liver maturity status is a critical parameter for the evaluation of DILI.

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Study on early biomarkers of zebrafish liver injury induced by acetaminophen

Cited by 11 publications

References 43 publications

NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity

NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

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