Protective effect of geranylgeranylacetone on trinitrobenzene sulfonic acid-induced colitis in mice

• Published in: International journal of molecular medicine Vol. 17; no. 2; pp. 229 - 234
• Main Authors: Ohkawara, Tatsuya, Nishihira, Jun, Takeda, Hiroshi, Katsurada, Takehiko, Kato, Kanji, Yoshiki, Takashi, Sugiyama, Toshiro, Asaka, Masahiro
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-02-2006
• Subjects: Animals; Body Weight - drug effects; CD4-Positive T-Lymphocytes - drug effects; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Colitis - prevention & control; Diterpenes - pharmacology; HSP70 Heat-Shock Proteins - metabolism; Male; Mice; Mice, Inbred BALB C; Organ Size - drug effects; Peroxidase - metabolism; Survival Rate; Trinitrobenzenesulfonic Acid - pharmacology
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.17.2.229

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.