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 B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 microg/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 AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-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 AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-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 AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.
Liu
J
J
Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore.
Yang
C F
CF
Wasser
S
S
Shen
H M
HM
Tan
C E
CE
Ong
C N
CN
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D008516:Medicine, Chinese Traditional; D010936:Plant Extracts; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D027561:Salvia miltiorrhiza
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D018736:DNA Adducts; D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D007527:Isoenzymes; D010936:Plant Extracts; D012333:RNA, Messenger; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D016604:Aflatoxin B1; C112500:glutathione S-transferase 9.5-1; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine