Hepatic lipid metabolism disorders and immunotoxicity induced by cysteamine in early developmental stages of zebrafish.

Animals Zebrafish / metabolism Cysteamine / toxicity Lipid Metabolism Biotinidase / metabolism Liver Lipid Metabolism Disorders / metabolism Oxidative Stress Triglycerides / metabolism Chemical and Drug Induced Liver Injury / pathology
Cysteamine Inflammation Lipid metabolism Liver Pantetheinase Zebrafish

Journal

Toxicology
ISSN: 1879-3185
Titre abrégé: Toxicology
Pays: Ireland
ID NLM: 0361055

Informations de publication

Date de publication:
07 2023
Historique:
received: 16 04 2023
revised: 13 05 2023
accepted: 23 05 2023
medline: 16 6 2023
pubmed: 27 5 2023
entrez: 26 5 2023
Statut: ppublish

Résumé

Cysteamine, a sulfhydryl compound, is an intermediate in the metabolism of coenzyme A to taurine in living organisms. However, the potential side effects of cysteamine such as hepatotoxicity in pediatric patients have been reported in some studies. To evaluate the impact of cysteamine on infants and children, larval zebrafish (a vertebrate model) were exposed to 0.18, 0.36 and 0.54 mM cysteamine from 72 hpf to 144 hpf. Alterations in general and pathological evaluation, biochemical parameters, cell proliferation, lipid metabolism factors, inflammatory factors and Wnt signaling pathway levels were examined. Increased liver area and lipid accumulation were observed in liver morphology, staining and histopathology in a dose-dependent manner with cysteamine exposure. In addition, the experimental cysteamine group exhibited higher alanine aminotransferase, aspartate aminotransferase, total triglyceride and total cholesterol levels than the control group. Meanwhile, the levels of lipogenesis-related factors ascended whereas lipid transport-related factors descended. Oxidative stress indicators such as reactive oxygen species, MDA and SOD were upregulated after cysteamine exposure. Afterwards, transcription assays revealed that biotinidase and Wnt pathway-related genes were upregulated in the exposed group, and inhibition of Wnt signaling partially rescued the abnormal liver development. The current study found that cysteamine-induced hepatotoxicity in larval zebrafish is due to inflammation and abnormal lipid metabolism, which is mediated by biotinidase (a potential pantetheinase isoenzyme) and Wnt signaling. This provides a perspective on the safety of cysteamine administration in children and identifies potential targets for protection against adverse reactions.

Identifiants

DOI: 10.1016/j.tox.2023.153555 PMID: 37236339
pubmed: 37236339
pii: S0300-483X(23)00141-5
doi: 10.1016/j.tox.2023.153555
pii:
doi:

Substances chimiques

Cysteamine 5UX2SD1KE2
Biotinidase EC 3.5.1.12
Triglycerides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

153555

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

Chao Chen (C)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.

Yuhua Zuo (Y)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China.

Hongmei Hu (H)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China.

Xue Li (X)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China.

Li Zhang (L)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China.

Dou Yang (D)

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.

Fasheng Liu (F)

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.

Xinjun Liao (X)

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.

Guanghua Xiong (G)

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.

Zigang Cao (Z)

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China.

Zilin Zhong (Z)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China.

Yanlong Bi (Y)

Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China. Electronic address: biyanlong@tongji.edu.cn.

Huiqiang Lu (H)

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, Jiangxi, China. Electronic address: Luhuiqlang@jgsu.edu.cn.

Jianjun Chen (J)

Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China. Electronic address: chenjianjun@tongji.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Thiols › Aminoéthanethiols › Mercaptamine › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Amidohydrolases › Biotinidase › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Système digestif › Foie › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme lipidique › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Phénomènes physiologiques › Stress physiologique › Stress oxydatif › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Lipides › Glycérides › Triglycéride › Hepatic lipid metabolism disorders and...
questionsmedicales.fr › Troubles dus à des produits chimiques › Intoxication › Lésions hépatiques dues aux substances › Hepatic lipid metabolism disorders and...