Effect of sodium ozagrel on the activity of rat CYP2D6.

Effect of sodium ozagrel on the activity of rat CYP2D6. Research Abstract Details 

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Effect of sodium ozagrel on the activity of rat CYP2D6. Abstract Text:

Hong Wu,Weijiang Yu,Lijun Huang,Jing Wang,Xiaobo Tang,Wei Yang,Yan Liu,Huiyan Yu,Daling Zhu,

The aim of the study was to investigate the influence of sodium ozagrel on CYP2D6 (cytochromeP450 2D6) activity. The studies were performed with rat urine and liver microsomes and chemical inhibitors. The metabolism of dextromethorphan (dextrophan/dextromethorphan, dextrophan is a metabolite of dextromethorphan) and phenacetin (paracetamol/phenacetin, paracetamol is a metabolites of phenacetin) was used as probe to measure CYP2D6 and CYP1A2 (cytochromeP450 1A2) activity, respectively, determined by high-performance liquid chromatography (HPLC). The results showed that the metabolism of dextrophan/dextromethorphan in the sodium ozagrel-treated group (37 mg/kg) was higher than that of the control (P<0.05/6) in both in vivo and in vitro studies (r=0.9811). The rate of dextromethorphan metabolism was inhibited by sodium ozagrel and cimetidine in rat liver microsomes prepared from sodium ozagrel-treated rats and control rats group (sodium ozagrel IC(50)=26.5 microM, cimetidine IC(50)=86.3 microM in sodium ozagrel-treated group; sodium ozagrel IC(50)=13.9 microM, cimetidine IC(50)=24.8 microM in control group). The inhibitory effect of sodium ozagrel on CYP2D6 activity was noncompetitive with dextromethorphan with a K(i) of 324.94 microM. Kinetic parameters of the reactions were established by using Lineweaver-Burk with K(m)=0.67 mM and V(max)=2.13 pm/min/mg protein for the sodium ozagrel-treated group and K(m)=0.29 mM, and V(max)=0.91 pm/min/mg protein for the control group, respectively. The expression of CYP2D6 protein in the treated group was higher than that of the control group, as determined by Western blotting. The activity and expression of CYP1A2 did not show obvious differences in the control group and sodium ozagrel treated group. In conclusion, sodium ozagrel metabolism in rats is mediated primarily through CYP2D6, and sodium ozagrel can induce CYP2D6 activity.

Effect of sodium ozagrel on the activity of rat CYP2D6. Publishing Authors By Initials

H Wu,W Yu,L Huang,J Wang,X Tang,W Yang,Y Liu,H Yu,D Zhu,

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Effect of sodium ozagrel on the activity of rat CYP2D6. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: European journal of pharmacology

VOLUME: 573

Page Numbers: 55-9

Journal Abbreviation: Eur. J. Pharmacol.

ISSN: 0014-2999

DAY: 4

MONTH: 07

YEAR: 2007

Effect of sodium ozagrel on the activity of rat CYP2D6. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Effect of sodium ozagrel on the activity of rat CYP2D6.

AFFILIATION: College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; Mudanjiang Medical College, Mudanjiang 157011, PR China.

Country: Netherlands

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MEDLINETA: Eur J Pharmacol

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