Inhibition by Gomisin A, a Lignan Compound, of Hepatocarcinogenesis by 3'-Methyl-4-dimethylaminoazobenzene in Rats

• Published in: Biological & pharmaceutical bulletin 1994/06/15, Vol.17(6), pp.808-814
• Main Authors: OHTAKI, Yumiko, NOMURA, Masaaki, HIDA, Tatsuhito, MIYAMOTO, Kenichi, KANITANI, Masanao, AIZAWA, Tatsuo, ABURADA, Masaki
• Format: Article
• Language: English
• Subjects: 3'-methyl-4-dimethylaminoazobenzene; Animals; Cell Division - drug effects; Cell Nucleus - drug effects; chemoprevention; Cyclooctanes; Diet; Dioxoles - pharmacology; Dioxoles - therapeutic use; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Electrophoresis, Polyacrylamide Gel; Flow Cytometry; glutathione S-transferase; Glutathione Transferase - metabolism; gomisin A; hepatocarcinogenesis; Immunoblotting; Immunohistochemistry; Isoenzymes - metabolism; Lignans; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver Neoplasms - chemically induced; Liver Neoplasms - prevention & control; Male; Methyldimethylaminoazobenzene - pharmacokinetics; Methyldimethylaminoazobenzene - toxicity; Ploidies; ploidy analysis; Protein Binding - drug effects; Rats
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.17.808

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.