Effects of Sho-Saiko-to on hepatocarcinogenesis and 8-hydroxy-2'-deoxyguanosine formation.
Oxidative stress plays an important role in hepatocarcinogenesis. Although Sho-saiko-to (TJ-9), a Japanese herbal medicine which has been recently administered to patients with chronic liver disease in Japan, prevents hepatocarcinogenesis, the mechanism by which TJ-9 protects against cancer development is not fully understood. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a DNA adduct by reactive oxygen species, is known as a parameter of genetic risk for hepatocarcinogenesis. To clarify whether the preventive effect on hepatocarcinogenesis by TJ-9 is dependent on 8-OHdG, the effect on 8-OHdG levels by TJ-9 was examined by using high-performance liquid chromatography-mass spectrometry (LC-MS) in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model of male Fisher rats. TJ-9 reduced the number of preneoplastic cells, detected as the glutathione S transferase P (GST-P)-positive hepatocytes, and inhibited the development of liver tumors. TJ-9 also significantly decreased the formation of 8-OHdG, as indicated by LC-MS and immunohistochemical analysis. In addition, ornithine decarboxylase (ODC) activity and the number of proliferating cell nuclear antigen (PCNA)-positive cells were not altered. An electron paramagnetic resonance spin-trapping technique showed that TJ-9 scavenges hydroxyl radicals in a dose-dependent manner. In conclusion, the results of the present study suggest that TJ-9 prevents hepatocarcinogenesis in association with inhibition of 8-OHdG formation.
Shiota
Goshi
G
Second Department of Internal Medicine, Tottori University, Yonago, Japan. gshiota@grape.med.tottori-u.ac.jp
Maeta
Yoshiko
Y
Mukoyama
Tomoyuki
T
Yanagidani
Atsushi
A
Udagawa
Akihide
A
Oyama
Kenji
K
Yashima
Kazuo
K
Kishimoto
Yosuke
Y
Nakai
Yoichiro
Y
Miura
Tetsuo
T
Ito
Hisao
H
Murawaki
Yoshikazu
Y
Kawasaki
Hironaka
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D002452:Cell Count; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000032:analysis; D017665:Hydroxyl Radical / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009955:Ornithine Decarboxylase / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D004365:Drugs, Chinese Herbal; D018809:Proliferating Cell Nuclear Antigen; D017665:Hydroxyl Radical; C018142:saiko-keishi-to; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D009955:Ornithine Decarboxylase; D003849:Deoxyguanosine