Protective effect of geranylgeranylacetone on trinitrobenzene sulfonic acid-induced colitis in mice.
Geranylgeranylacetone (GGA) has recently been reported to have a protective effect against ischemic, injurious and apoptotic stress in several tissues. The aim of this study was to determine the effect of GGA on colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Colitis was induced by intrarectal instillation of TNBS in 50% ethanol in BALB/c mice. Survival, change in body weight and change in wet colon weight were assessed. Histological score in the colon was evaluated 5 days after TNBS treatment. The level of myeloperoxidase (MPO) activity in the colon was also determined. Immunohistochemistry for CD4 in the colon was performed. In addition, the level of heat shock protein (HSP) 70 in the colon was determined by Western blot analysis. Mice were orally treated with GGA (300 mg/kg) 2 h before and every other day after starting TNBS administration. Treatment with GGA markedly improved the survival rate, and reduced the loss of body weight and loss of wet colon weight in mice with TNBS-induced colitis. GGA also suppressed the increase in MPO activity and the number of CD4-positive cells infiltrating the colons of mice with TNBS-induced colitis. Furthermore, treatment with GGA remarkably up-regulated the expression of HSP70 in the colons of mice with TNBS-induced colitis. Our results provide further evidence that GGA has therapeutic potential for intestinal inflammation.
Ohkawara
Tatsuya
T
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. tokawara@med.hokudai.ac.jp
Nishihira
Jun
J
Takeda
Hiroshi
H
Katsurada
Takehiko
T
Kato
Kanji
K
Yoshiki
Takashi
T
Sugiyama
Toshiro
T
Asaka
Masahiro
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D015996:Survival Rate; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; C031049:geranylgeranylacetone