Protection of Salvia Miltiorrhiza against aflatoxin-B 1-induced hepatocarcinogenesis in Fischer 344 rats : Dual mechanisms involved

Abstract

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 μg/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 1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.