RESUMO
OBJECTIVE: To compare the effect on CYP450 isoenzyme in rats with acute liver injury induced by different chemicals. METHODS: Acute liver injury model of rats induced by tetrachloromethane(CCl4), D-aminogalactose(D-GalN)/lipopolysaccharide(LPS), α-naphthyl isothiocyanate(ANIT) respectively whereas the normal Wistar rats were used as controls. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the blood samples were collected from the fundus venous plexus of rat at different time point, the blood drug concentration of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK Solutions 2™. Compared with normal rats, the changes of the probe drug pharmacokinetics in different rat models were used as the basis for the evaluation of the metabolic activity of CYP450 isoenzyme. RESULTS: Compared with normal rats, the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 of CCl4 group rats were significantly inhibited, and the activities of CYP3A4 was slightly inhibited; the activities of CYP2C9, CYP2D6 and CYP3A4 of D-GalN/LPS group rats were significantly induced, and the activity of CYP2D6 and CYP3A4 was slightly induced, and the activity of CYP1A2 was not significantly affected, but the activity of CYP2C19 was significantly inhibited; the activities of CYP2C9, CYP2C19 and CYP3A4 of ANIT group rats were significantly induced, the activity of CYP3A4 were slightly induced, and the activity of CYP2D6 was not significantly affected, but the activity of CYP1A2 was significantly inhibited. CONCLUSION: There are significant differences in the activities of CYP450 isoenzyme in the rat model of acute liver injury induced by different chemicals.
RESUMO
AIM:To evaluate the therapeutic effects of bisdemethoxycurcumin liposome in mice with CCl4-induced acute liver injury model and its mechanism.METHODS:40 ICR mice were randomly divided into 4 groups:control group,model group,bisdemethoxycurcumin injection group and demethoxycurcumin liposome group(n=10).The liver injury model was made by injecting CCl4 in mouse's abdomen.The activities of ALT,AST in serum,the contents of MDA in liver and the pathological changes of hepatic tissue were investigated.RESULTS:Compared with those in control group,the serum ALT,AST activities and liver MDA contents of model group were highly increased,but those in bisdemethoxycurcumin injection group and bisdemethoxycurcumin liposome group were reduced significantly.The liver lobules were ameliorated obviously too,especially in bisdemethoxycurcumin liposome group.The pharmacodynamic action of liposome was better than that of the injection.CONCLUSION:Bisdemethoxycurcumin liposome has significantly protective effects on CCl4-induced acute chemical liver injury by reducing peroxidation of lipid in endotheliocyte of the liver.