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Hepatic lipid metabolism disorders and immunotoxicity induced by cysteamine in early developmental stages of zebrafish.
Chen, Chao; Zuo, Yuhua; Hu, Hongmei; Li, Xue; Zhang, Li; Yang, Dou; Liu, Fasheng; Liao, Xinjun; Xiong, Guanghua; Cao, Zigang; Zhong, Zilin; Bi, Yanlong; Lu, Huiqiang; Chen, Jianjun.
Afiliación
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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,
  • 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,
  • 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,
  • 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,
  • 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,
  • 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
  • Bi Y; Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China. Electronic address: biyanlong@tongji.edu.cn.
  • 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,
  • 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
Toxicology ; 493: 153555, 2023 07.
Article en En | MEDLINE | ID: mdl-37236339
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos del Metabolismo de los Lípidos / Enfermedad Hepática Inducida por Sustancias y Drogas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicology Año: 2023 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos del Metabolismo de los Lípidos / Enfermedad Hepática Inducida por Sustancias y Drogas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Toxicology Año: 2023 Tipo del documento: Article Pais de publicación: Irlanda