Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress.
- Author:
Yu-xin ZANG
;
Bing-ting SUN
;
Wen-zhu ZHAO
;
Na RONG
;
Guo-liang DAI
;
Wen-zheng JU
;
Heng-shan TAN
- Publication Type:Journal Article
- MeSH:
Animals;
Chlorzoxazone;
metabolism;
Chromatography, Liquid;
Cytochrome P-450 Enzyme System;
metabolism;
Depression;
Dextromethorphan;
metabolism;
Liver;
enzymology;
Midazolam;
metabolism;
Omeprazole;
metabolism;
Rats;
Stress, Physiological;
Tandem Mass Spectrometry;
Theophylline;
metabolism;
Tolbutamide;
metabolism
- From:
Acta Pharmaceutica Sinica
2015;50(3):319-325
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
