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.
Ohtaki
Y
Y
Research Laboratory for Development of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Nomura
M
M
Hida
T
T
Miyamoto
K
K
Kanitani
M
M
Aizawa
T
T
Aburada
M
M
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