Geranylgeranylacetone protects mice from dextran sulfate sodium-induced colitis.
OBJECTIVE
Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice.


METHODS
BALB/c mice were given 3% DSS solution orally for 7 days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7 days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50-500 mg/kg) when treatment of DSS started.


RESULTS
It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-alpha and IFN-gamma induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS.


CONCLUSIONS
Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.
Ohkawara
Tatsuya
T
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. tokawara@med.hokudai.ac.jp
Nishihira
Jun
J
Takeda
Hiroshi
H
Miyashita
Kencho
K
Kato
Kanji
K
Kato
Mototsugu
M
Sugiyama
Toshiro
T
Asaka
Masahiro
M
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012720:Severity of Illness Index
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006360:Heat-Shock Proteins; D016264:Dextran Sulfate; C031049:geranylgeranylacetone