Protective effect of Juzen-taiho-to on hepatocarcinogenesis is mediated through the inhibition of Kupffer cell-induced oxidative stress
Masato Tsuchiya
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Search for more papers by this authorCorresponding Author
Hiroshi Kono
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Fax: +055-273-7390.
First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, JapanSearch for more papers by this authorMasanori Matsuda
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Search for more papers by this authorHideki Fujii
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Search for more papers by this authorIvan Rusyn
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
Search for more papers by this authorMasato Tsuchiya
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Search for more papers by this authorCorresponding Author
Hiroshi Kono
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Fax: +055-273-7390.
First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, JapanSearch for more papers by this authorMasanori Matsuda
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Search for more papers by this authorHideki Fujii
First Department of Surgery, University of Yamanashi, Chuo, Yamanashi Prefecture, Japan
Search for more papers by this authorIvan Rusyn
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
Search for more papers by this authorAbstract
Traditional herbal formulations, such as Juzen-taiho-to (TJ-48), are used extensively in medical practice in Asia even though their mechanism of action remains elusive. This study tested a hypothesis that TJ-48 is protective against hepatocarcinogenesis by impeding Kupffer cell-induced oxidative stress. Forty-eight patients were randomly assigned to receive TJ-48 (n = 10), or no supplementation (n = 38) for up to 6 years after surgical treatment for hepatocellular carcinoma (HCC). In addition, to investigate the mechanism of protective action of TJ-48, diethylnitrosamine-containing water was administered for 22 weeks to male mice that were fed regular chow or TJ-48-containing diet. Liver tumor incidence, cell proliferation, number of 8-hydroxy-2′-deoxyguanosine- or F4/80-positive cells, and cytokine expression were evaluated. Although most of the patients experienced recurrence of HCC, a significantly longer intrahepatic recurrence-free survival was observed in the TJ-48 group. In mice, TJ-48 inhibited the development of liver tumors, reduced oxidative DNA damage, inflammatory cell infiltration and cytokine expression. Administration of TJ-48 improves intrahepatic recurrence-free survival after surgical treatment of hepatocellular carcinoma. On the basis of animal experiments, we reason that the protective mechanism of TJ-48 involves inhibition of Kupffer cells. This leads to lower levels of pro-inflammatory cytokines and oxidants in liver which may slow down the process of hepatocarcinogenesis and improves hepatic recurrence-free survival in patients with HCC. © 2008 Wiley-Liss, Inc.
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