Inhibition by gomisin A, a lignan compound, of hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene in rats.
The effects of gomisin A, a lignan compound of Schizandra fruits, on hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in rats were investigated. Gomisin A inhibited both increases of the number and size of glutathione S-transferase placental form (GST-P)-positive foci, a marker enzyme of preneoplasm, and the population of diploid nuclei, as a proliferative state of hepatocytes, in the liver from rats simultaneously treated with 3'-MeDAB. Gomisin A increased GST activity in the liver, by raising the level of GST 1 and 2 isozymes. 3'-MeDAB increased GST activity and GST-P expression. This high level of GST-P induced by 3'-MeDAB was suppressed by additional treatment with gomisin A. In an experiment on simultaneous treatment, gomisin A increased the biliary excretion of 3'-MeDAB-related aminoazo dyes and decreased the content in the liver of rats fed with 0.06%-3'-MeDAB containing diet. In an experiment on pretreatment with 3'-MeDAB, even though no aminoazo dye was detectable in the liver or bile 2-weeks after cessation of 3'-MeDAB-feeding, gomisin A showed a tendency to reduce the preneoplastic changes of increases in GST-P positive foci and diploid nuclei in the liver. These results suggest that gomisin A inhibits the hepatocarcinogenesis induced by 3'-MeDAB by enhancing the excretion of the carcinogen from the liver and by reversing the normal cytokinesis.
Research Laboratory for Development of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Y
Y
Ohtaki
M
M
Nomura
T
T
Hida
K
K
Miyamoto
M
M
Kanitani
T
T
Aizawa
M
M
Aburada
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D034242:Cyclooctanes; D004032:Diet; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D017705:Lignans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000493:pharmacokinetics / Q000633:toxicity*; D011003:Ploidies; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
D034242:Cyclooctanes; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D017705:Lignans; D008749:Methyldimethylaminoazobenzene; C033585:schizandrol B; D005982:Glutathione Transferase