Protection of Salvia Miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats -: Dual mechanisms involved

Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B-1 (AFB(1))-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB(1) (40 mug/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB(1) exposure, Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB(1) dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB(1)-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB(1), which clearly suggests that SM is effective in preventing AFB(1)-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB(1) hepatocarcinigenesis was associated with a corresponding decrease in AFB(1)-DNA adducts formation as well as AFB(1)-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver, Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB, detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM. (C) 2001 Elsevier Science Inc. All rights reserved.