Effects Of Glycyrrhetic Acid Solid Dispersions On Liver Injury Induced By Cadmium In Rats

Objectives To prepare solid dispersions of glycyrrhetic acid(GA) with polyvinylpyrrolidone K30( PVP K30) to improve the solubility and bioavailability of GA and to observe the effscts of GA solid dispersion on liver injury induced by cadmium in rats.Methods 1 Solid dispersion of GA was prepared by solvent method with PVP K30 as carrier. And the best proportion of GA to PVP K30 has been optimized. The GA-PVP solid dispersion was analyzed by solubility test, differential scanning calorimetry(DSC), and infrared spectroscopy(IR). 2 Male SD rats(n=16) were randomly divided into 2 groups(n= 8). The rats were administrated GA and GA-PVP solid dispersions respectively in order that all rats were fed same GA dose(50 mg·kg-1). The concentration of chrysophanol in plsma were determined by high performance liquid chromatography(HPLC) to calculate the pharmacokinetic parameters. 3 Male SD rats(n=30) were randomly divided into 5 groups(n=6) including blank group, cadmium exposure group, GA group, GA solid dispersion(GA-SD) group, and Ganlixin(GL) group. The liver injury model was established by Cd Cl2. All rats were intraperitoneal administered Cd Cl22 mg·kg-1by giving every other day for 6 times except the blank. While rats in the blank group was given purified water. At the same time, the rats of GA group, GA-SD group and GL group were intervened by GA, GA solid dispersion and Ganlixin respectively, once a day for six weeks.After the last administration the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), superoxide dismutase(SOD), glutathione(GSH), and malondialdehyde( MDA) were determined.Results 1 Optimum proportion of GA to PVP K30 was 1:2. Solubility rate of GA in the solid dispersion was more than the original one. The results of DSC and IR showed that GA solid dispersion was formed,and hydrogen bond might have been formed between GA and PVP K30. 2 The concentration-time profiles of GA and its solid dispersion showed the enterohepatic circulation of GA. Their AUC and Cmaxfor GA group were(35.96±0.6)μg·h·m L-1 and(2.56±0.09)μg·L-1, significant different from those of GA solid dispersions group[(71.59±1.61) μg·h·m L-1and(4.82±0.24)μg·L-1)] 3 The levels of ALT, AST, MDA, GSH in cadmium exposure group were higher than those in blank group(P<0.05). And the levels of SOD was lower, and the difference was significant(P<0.05).Our data indicated that the liver injury model was successfully established. The effect of GA-SD on the above index and the levels of GSH, SOD were siginificant from those of GA group and GL group(P<0.05). The level of ALT, AST, MDA of GA-SD group were significant from those of GA group(P< 0.05). Data processing: using SPSS statistics V17.0 statistical software for data analysis of variance and LSD test. Data are used(x ±s)said. Among groups using ANOVA test, between two groups using independent sample LSD test.Conclusions 1 The GA solid dispersion with PVP K30 as the carrier are succeed made and our founding proves that it can increase the bioavailability of chrysophanol in rats. 2GA solid dispersion alleviate the liver injure in rats induced by cadmium exposure.