Abstract | AIM: METHODS: We allocated 6-wk-old male F344 rats to choline-supplemented, L- amino acid-defined (CSAA) diet (control group), CSAA diet + Y-40138 (control + Y-40138 group), choline-deficient, L- amino acid-defined ( CDAA) diet (NASH group), or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group, we measured the plasma alanine aminotransferase (ALT) levels, and the plasma and liver levels of tumor necrosis factor-alpha ( TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10). Tissue specimens of phosphate buffered saline-perfused liver were subjected to hematoxylin and eosin staining, Azan staining, Sirius red staining, and immunohistochemical staining (for Kupffer cells and TNF-alpha). We then extracted Kupffer cells from the collagenase-perfused livers using the Percoll gradient centrifugation method, and measured the TNF-alpha levels in the supernatant (in vitro TNF-alpha production by Kupffer cells) using an enzyme-linked immunosorbent assay kit. RESULTS: In comparison to the NASH group, serum ALT elevation was mild, production of serum and liver TNF-alpha and IFN-gamma was inhibited, and IL-10 production was increased in the NASH + Y-40138 group. Amelioration of liver histology was also noted in the NASH + Y-40138 group. Kupffer cell immunohistochemical staining revealed no differences between groups, whereas TNF-alpha immunohistochemical staining showed fewer stained cells in the NASH + Y-40138 group than in the NASH group. The TNF-alpha levels in the in-vitro Kupffer cell culture supernatant were lower in the NASH + Y-40138 group than in the NASH group. CONCLUSION: Administration of Y-40138 to NASH model rats reduced hepatic inflammation and suppressed fibrosis. These results indicate that the multiple cytokine production modulator, Y-40138, is promising as a novel treatment for NASH.
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Authors | Tatsuhiro Tsujimoto, Hideto Kawaratani, Toshiyuki Kitazawa, Hitoshi Yoshiji, Masao Fujimoto, Masahito Uemura, Hiroshi Fukui |
Journal | World journal of gastroenterology
(World J Gastroenterol)
Vol. 15
Issue 44
Pg. 5533-40
(Nov 28 2009)
ISSN: 2219-2840 [Electronic] United States |
PMID | 19938191
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetamides
- Cytokines
- Piperazines
- Tumor Necrosis Factor-alpha
- Y 39041
- Interleukin-10
- Interferon-gamma
- Alanine Transaminase
- Collagenases
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Topics |
- Acetamides
(pharmacology)
- Alanine Transaminase
(blood)
- Animals
- Collagenases
(chemistry)
- Cytokines
(antagonists & inhibitors, blood)
- Enzyme-Linked Immunosorbent Assay
(methods)
- Fatty Liver
(therapy)
- Immunohistochemistry
(methods)
- Immunotherapy
(methods)
- Interferon-gamma
(blood)
- Interleukin-10
(blood)
- Kupffer Cells
(drug effects)
- Male
- Piperazines
(pharmacology)
- Rats
- Rats, Inbred F344
- Tumor Necrosis Factor-alpha
(blood)
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