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Non-alcoholic fatty liver disease changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats.
Shen, Yifei; Liu, Jie; Yao, Bingyi; Zhang, Yuanjin; Huang, Shengbo; Liang, Chenmeizi; Huang, Junze; Tang, Yu; Wang, Xin.
Afiliación
  • Shen Y; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Liu J; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Yao B; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Zhang Y; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Huang S; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Liang C; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Huang J; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Tang Y; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
  • Wang X; Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China. Electronic address: xwang@bio.ecnu.edu.cn.
Toxicol Lett ; 396: 36-47, 2024 May 15.
Article en En | MEDLINE | ID: mdl-38663832
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, which can cause serious complications and gradually increase the mortality rate. However, the effects of NAFLD on drug-metabolizing enzymes and transporters remain unclear, which may cause some confusion regarding patient medication. In this study, a NAFLD rat model was constructed by feeding rats with methionine and choline deficiency diets for 6 weeks, and the mRNA and protein levels of drug-metabolizing enzymes and transporter were analyzed by real-time fluorescent quantitative PCR and Western blot, respectively. The activity of drug-metabolizing enzymes was detected by cocktail methods. In the NAFLD rat model, the mRNA expression of phase I enzymes, phase II enzymes, and transporters decreased. At the protein level, only CYP1A1, CYP1B1, CYP2C11, and CYP2J3 presented a decrease. In addition, the activities of CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP3A2, UGT1A1, UGT1A3, UGT1A6, and UGT1A9 decreased. These changes may be caused by the alteration of FXR, HNF4α, LXRα, LXRß, PXR, and RXR. In conclusion, NAFLD changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats, which may affect drug metabolism and pharmacokinetics. In clinical medication, drug monitoring should be strengthened to avoid potential risks.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deficiencia de Colina / Ratas Sprague-Dawley / Sistema Enzimático del Citocromo P-450 / Enfermedad del Hígado Graso no Alcohólico / Hígado Límite: Animals Idioma: En Revista: Toxicol Lett Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deficiencia de Colina / Ratas Sprague-Dawley / Sistema Enzimático del Citocromo P-450 / Enfermedad del Hígado Graso no Alcohólico / Hígado Límite: Animals Idioma: En Revista: Toxicol Lett Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos