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Difference in hepatotoxicity of furan-containing components in cortex dictamni correlates the efficiency of their metabolic activation.
Pan, Jie; Wu, Chutian; Tan, Rong; Liao, Yufen; Zhao, Guode; Li, Wei; Peng, Ying; Li, Weiwei; Zheng, Jiang.
Afiliação
  • Pan J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; School of Pharmacy, Guiz
  • Wu C; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.
  • Tan R; School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.
  • Liao Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.
  • Zhao G; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
  • Li W; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
  • Peng Y; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China. Electronic address: yingpeng1999@163.com.
  • Li W; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; Engineering Research Center fo
  • Zheng J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; School of Pharmacy, Guizhou Medical University, Guiyang, Guizhou 550004, PR China; Engineering Research Center fo
Phytomedicine ; 114: 154778, 2023 Jun.
Article em En | MEDLINE | ID: mdl-36996529
ABSTRACT

BACKGROUND:

Cortex Dictamni (CD) has been associated with an increased risk of liver injury, which may be attributable to the metabolic activation of its furan-containing components (FCC). However, the hepatotoxic potencies of these FCCs and the mechanisms behind the differences in their toxicity intensity remain unknown.

METHODS:

The constituents of CD extract were determined by LC-MS/MS. Potentially toxic FCCs were screened by a previously published method. Hepatotoxicity of potentially toxic FCCs was evaluated in cultured mouse primary hepatocytes and mice. The ability to deplete hepatic glutathione (GSH), along with the formation of the corresponding GSH conjugates, resulting from the metabolic activation was determined ex vivo in mice. Intrinsic clearance rates (CLint,Vmax/Km) were assessed by a microsome-bases assay.

RESULTS:

A total of 18 FCCs were detected in CD extract. Among them, four FCCs, including rutaevin (RUT), limonin (LIM), obacunone (OBA) and fraxinellone (FRA) were found to be bioactivated in microsomal incubations. Only FRA displayed significant hepatotoxicity in vitro and in vivo. Similarly, FRA caused GSH depletion and GSH conjugation the most in vivo. The order of CLint for the four FCCs was FRA>>OBA>LIM>RUT.

CONCLUSION:

FRA is the major toxic FCC component of hepatotoxic CD extract. The hepatotoxicity of FCCs is closely related to the efficiency of their metabolic activation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espectrometria de Massas em Tandem / Doença Hepática Induzida por Substâncias e Drogas Limite: Animals Idioma: En Revista: Phytomedicine Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espectrometria de Massas em Tandem / Doença Hepática Induzida por Substâncias e Drogas Limite: Animals Idioma: En Revista: Phytomedicine Ano de publicação: 2023 Tipo de documento: Article