Liver Detoxification Of Genistein And Its Effect On The Regulation Of UGTs Activity

Objective:Soy Isoflavones(SI) is a class of secondary metabolites in the process of soybean growth. It has been found that it has a variety of biological functions. Uridine diphosphate glucuronyltransferase (UGTs) is the most important phase II metabolic enzymes in the body. The purpose of this study is to investigate the detoxification of soy isoflavones and the effect of soy isoflavones on the activity of UGTs.Methods:Mice were treated by genistein and glucurone before using a large doses of acetaminophen to make these mice liver injury. The biochemical indicators such as the activities of ALT AST LDH and the contents of ALB TP GSH were detected in serum and in liver, the impact of genistein and glucurone on liver injuried mice were observed through theses biochemical indicators. The protective effect of genistein and glucurone on liver damage in mice were compared.The mRNA expression of liver UGTs isozyme were assayed by RT-PCR. The liver microsomes induced by genistein were used to incubation in vitro, the activity of UGTs in this incubation system were detected,and then the metabolism of acetaminophen in vitro incubation reaction were inspected.Results:(1) Compared with model group(APAP), genistein or associated with glucurone could reduce the activity of ALT AST LDH, improve the content of TP ALB GSH significantly. These indicators were close to the control group. The effect was not obvious when the glucurone was used alone.(2) The mRNA expression of UGT1A1UGT1A5UGT1A10UGT2B1were significantly increased in the genistein or associated with glucurone groups compared to that in the blank and model group.(3) Genistein can reduce the content of acetaminophen in mice blood, increase the activity of UGTs, and improve the metabolism of acetaminophen in vitro reaction.Conclusion:Genistein has the protective effect on mice liver injury caused by acetaminophen, The mechanism of the protective of genistein was related to that genistein can increase the mRNA expression of UGT1A1,UGT1A5, UGT1A10and UGT2B1.Genistein could increase the activity of UGTs to strengthen the metabolic inactivation pathway of APAP mediated by UGTs, and then the toxic effects of APAP was reduced.