The Effect Of Rat Liver Cytochrome P450 Enzyme Level On The Hepatotoxicity Of Polygonum Multiflorum

Objective:To investigate rat hepatic cytochrome P450 enzyme levels on Polygonum hepatotoxicity.Methods:Using male SD rats,200±10 g,were randomly divided into six groups:control group(a),Polygonum control group(b),CYP1A2 inhibition in the control group(c),CYP2E1 inhibition of the control group(d),Polygonum+CYP1A2 suppression group(e),Polygonum+CYP2E1 suppression group(f);Polygonum single gavage aqueous extract:c,e group at the start 5d administered intraperitoneally before Polygonum CYP1A2 inhibitors cimetidine 50mg/kg BW,d,f group fed Polygonum 2.5h before intraperitoneal injection of CYP2E1 inhibitors trans 1,2-dichloroethylene 100mg/kg BW,b,e,f group fed Polygonum single aqueous extract 40g/kg BW,and at 2h after administration,4h,24h,48h and 72h orbital blood;Long-term repeated intervals administered aqueous extract of Polygonum:c,e group fed Polygonum 5d ago at the beginning of CYP1A2 inhibitor,eimetidine intraperitoneal injection of 50mg/kg BW(continuous suppression interval,inhibit again,again interval,inhibit again)d,f before the group administered intraperitoneally Polygonum 2.5h CYP2E1 inhibitors of trans 1,2-dichloroethylene 100mg/kg BW(continuous suppression interval,again inhibition interval again,and again inhibition),b,e,f group was given water extract of Polygonum 40g/kg BW,continuous lw,interval 2w,again administered 1d,then the interval 3w,the administration again 3d,2h after each blood fed Polygonum rat liver transaminases AST and ALT activity was measured five kinds of liver microsomal cytochrome P450 enzyme activity,liver biopsy "cocktail"probe drugs and HE staining analysis of liver biopsy pathology.Results:Polygonum single gavage aqueous extract:Daily observations,measurements of body weight,rats appear lazy move,color is not China and other conditions,the weight loss within 24h;2h,4h,24h,48h,72h continuous determination of blood,ALT and AST liver transaminases within 24h of being affected significantly elevated ALT and AST in the 2h,4h,24h,respectively AST,significantly elevated ALT.Long-term repeated intervals administered aqueous extract of Polygonum:gavage significantly increased lw,ALT and AST,2w again dosing interval ld,ALT and AST were significantly higher again,again interval 3w,again administered 3d,ALT and AST again significantly increased;detect the activity of hepatic microsomal end of the experiment,the results of CYP1A2,CYP2E1,CYP2C9,CYP2D6 activity Polygonum control group were significantly lower,CYP1A2 CYP1A2 inhibitor activity was significantly lower in the control group,CYP2E1 inhibitor control group CYP2E1 and CYP2C9 activity was significantly reduced,Polygonum+CYP1A2 group mainly CYP1A2 and CYP2D6 activity down,Polygonum+CYP2E1 group mainly CYP2E1 and CYP2D6 activity down,and CYP3A4 enzyme activity increases;liver pathology analysis found that the rats with compared to the control groups,CYP1A2 or CYP2E1 inhibitor pretreatment plus Polygonum gavage treatment group had significant liver damage.Conclusions:Rat hepatic cytochrome P450 activity levels and Polygonum induced liver injury,liver cells inhibited the expression of CYP1A2 and CYP2E1 can cause acute liver toxicity in rats associated Polygonum.