Deoxycholic acid as an endogenous risk factor for hepatocarcinogenesis and effects of gomisin A, a lignan component of Schizandra fruits.
Although hepatocarcinogensis has been reported to be promoted by exogenous administration of bile acids, the relation of endogenous bile acids to hepatocarcinogenesis is not completely understood. This study investigates the relationship between serum concentration of bile acids, the appearance of preneoplastic change, glutathione S-transferase placental form (GST-P)-positive foci in the liver of male Donryu rats which had been fed 0.06% 3'-methyl-4-dimethylamino-azobenzene (3'-MeDAB), and the effects of gomisin A, previously reported to inhibit the tumor promotion process. During the feeding of 3'-MeDAB for 5 weeks, the concentrations of serum bile acids were found to have increased significantly to several times the levels found at the start of the experiment. The increase of serum bile acids, especially deoxycholic acid (DCA), and the appearance of preneoplastic lesions, the number and area of GST-P-positive foci in the liver, were significantly inhibited by simultaneous oral administration of gomisin A (30 mg/kg). When DCA (100 mg/kg) was orally administered after an initiation by 3'-MeDAB, serum bile acids and preneoplastic changes were significantly increased, these increases were inhibited by combined feeding of 0.03% gomisin A in the diet. There were good correlations between the serum concentration of DCA and the number of GST-P-positive foci in the liver in both experimental protocols. These results confirm that DCA is an endogenous risk factor for hepatocarcinogenesis and suggest that anti-promoter effect of gomisin A is based on improving metabolism of bile acids, including DCA.
Ohtaki
Y
Y
Faculty of Pharmaceutical Sciences, Hokuriku University, Tokyo, Japan.
Hida
T
T
Hiramatsu
K
K
Kanitani
M
M
Ohshima
T
T
Nomura
M
M
Wakita
H
H
Aburada
M
M
Miyamoto
K I
KI
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000097:blood*; D002273:Carcinogens; D003043:Cocarcinogenesis; D034242:Cyclooctanes; D003840:Deoxycholic Acid / Q000097:blood; D004149:Dioxoles / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D017705:Lignans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000097:blood* / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008749:Methyldimethylaminoazobenzene; D051381:Rats
D016588:Anticarcinogenic Agents; D001647:Bile Acids and Salts; D002273:Carcinogens; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D003840:Deoxycholic Acid; D008749:Methyldimethylaminoazobenzene; C033585:schizandrol B; D005982:Glutathione Transferase