ABSTRACT
Objective:To study the effect of Ginkgo biloba extract (EGb761) on metabolism of aflatoxin B_1(AFB_1) in Wistar rats. Methods:Seventy one Wistar rats were divided into three groups at random: group A (AFB_1 group), group B (AFB_1+EGb761 group), and group C (control group). The rats in groups A and B were given AFB_1(intraperitoneal injection, 100-200 μg/ kg body weight, 1-3 times/week). The rats in group B were fed the food containing EGb761 while the rats in groups A and C were given normal food. Blood samples were collected and liver biopsy was performed on the 14th, 28th and 42nd week. All the rats were sacrificed at the 64th week. The incidence of hepatoma was observed. The hepatic phase Ⅰ drug-metabolizing enzyme CYP450 and phase Ⅱ enzyme GST were detected by spectrometry. The serum AFB_1-lysine adduct was determined by high performance liquid chromatography (HPLC). The expression of 8-hydroxydeoxyguanosine(8-OHdG) was measured by immunohistochemistry. Results:The incidence of hepatocellular carcinoma (HCC) in group B was significantly lower than that in group A (26.92% vs 76.00%,P<0.001). No hepatocellular carcinoma developed in group C. EGb761 had no effects on the activities of CYP450 and GST in rat liver tissues. The level of AFB_1-lysine adduct reached the peak (4 356.01 pg/mg albumin) at the 14th week in group A. EGb761 significantly inhibited the formation of AFB_1-lysine adducts in serum by 13.07% at the 14th week (P＝0.033), and 73.63% at the 42nd week (P＝0.002). The expression of 8-OHdG protein in rat liver tissues in group B was significantly lower than that in group A at the 28th, 42nd, and 64th week (P<0.05). Conclusion:The main mechanism underlying the effect of EGb761 in blocking hepatogenesis induced by AFB_1 may not be fully related with its influence on the activity of liver phase Ⅰ and phase Ⅱ metabolizing enzymes. EGb761 inhibites the production of AFB_1-lysine addcuts, decreases the expression of 8-OHdG protein, and finally alleviates the DNA oxidative injury, which may be one of the mechanisms for the effects of EGb761 in inhibiting or delaying hepatogenesis induced by AFB_1.
ABSTRACT
Objective Using a short-term in vivo laboratory model of murine liver cancer induced with diethylnitrosamine (DEN),we inspected the impact of 5% C.Chrysantha leaves and 5% concentrations on induction of liver cancer with DEN.Methods Laboratory Winstar rats,all being male and SPF grade,were administered with the liver cancer initiator DEN(200?g/kg,ip,once only),then with murine food containing 0.015% 2-AAF (2-Acetaminoflueren) for 2 weeks,following an excision of the augmented parts as a selective promoting program that speeded up the proliferation of precancerous foci from the initiated hepatocytes.On the beginning of this experiment,5% C.Chrysantha leaves and 5% concentration-contained food were given to the trail rats; in contrast,normal food to the control.Rats were killed 3 days after feeding of 2-AAF-contained food.Targeting part of liver were collected for ?-glutamyltranspeptidase (?-GT) staining,and numbers and areas of?-GT positive foci per cm2 of the liver area were calculated using a software designed by us.Results Numbers and areas of?-GT positive foci of the trail are significantly less than those of the control.Conclusion 5% C.Chrysantha leaves and 5% concentrations inhibit the DEN induction to liver cancer.
ABSTRACT
Objective:To analyse the relationship between the expression of c myc,N ras oncogenes and hepatitis B Virus(HBV)infection in hepatocellular carcinoma(HCC) in Guangxi and the roles of these factors in hepatocarcinogenesis.Methods:c DNA RNA ,N ras mRNA,HBsAg and HBxAg in 40 cases of HCC and their adjacent liver tissues were studied.Rusults:The expression of c myc,N ras oncogenes were very high in HCC and their adjacent live tissues.Their positive rates were all over 85%.No significant difference of the two oncogenes′ expression among different grades of HCC was found.The positive rates of HBsAg and HBxAg were 87.09% and 79.31% respectively.The detections of oncogenes were parallel to the detections of HBsAg and HBxAg.Conclusion:c myc and N ras might be involved in the formation and maintenance of HCC.They may be activated by HBxAg.