2007 Fiscal Year Final Research Report Summary
Study about the elucidation of hepatocarcinogenesis mechanism km fatty liver and preventive strategies based on pathogenic considerations
| Project/Area Number |
18590574
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Tokai University |
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Principal Investigator |
WATANABE Tetsu Tokai University, Dep. of Community Health, Professor (10129744)
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| Co-Investigator(Kenkyū-buntansha) |
KINOUE Takaaki Tokai University, Dep. of Community Health, Associate Professor (30234313)
INAGAKI Yutaka Tokai University, Dep. of Community Health, Associate Professor (80193548)
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| Project Period (FY) |
2006 – 2007
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| Keywords | liver tumor / fatty liver / oxidative stress / FLS mouse / sodium butyrate / NF-κB / p21WAF |
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| Research Abstract |
We used FLS mice (n=48) in this study. FLS mouse develops spontaneously fatty liver chronically without obesity. Liver tumors develop after age of 1 year. The FLS mice were subdivided into three groups : group 1 received control diet (CA-1) alone, group 2 received diet containing lactobacillus, and group 3 received control diet containing clostridium butyricum that produce butyric acid in a bowel after oral intake.
At age 10 month, all mice showed significant fatty deposition in the liver without fibrosis. At age 12 month, 2 out of 8 mice in group 1 developed liver tumor, whereas 1 out of 8 mice developed liver tumor in both group 2 and 3. Measurement of short chain fatty acid in the feces by HPLC revealed that concentration of sodium butyrate increased in the mice of group 3.
Immunohistochemical analysis of the liver of 10-month-old LPS mice showed that 4-HNE, a marker of oxidative stress, remarkably increased in group 1 mice compared with those in group 3 mice. On the contrary, the protein expression of transcription factor NF-KB increased in the liver of group 3 mice by the Western blot analysis. Phosphorylation of c-jun (Ser 73) was also observed in the liver of mice in group 3. Finally, protein expression of p21 WAF1 also increased in the liver of group 3 mice by the Western blot.
These results indicate that oxidative stress takes a crucial role in the progression of liver disease in FLS mice. Oral intake of clostridium butyricum may protect the development of liver tumor in FLS mice.
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