Oxazolone-induced colitis in BALB/C mice: a new method to evaluate the efficacy of therapeutic agents for ulcerative colitis.
A number of experimental models of colitis have been proposed. However, few studies have presented T helper-2 (Th-2) type colitis models that substitute for human ulcerative colitis (UC). In recent years, the murine oxazolone (OXA)-induced colitis model came to be accepted as a Th-2 type model, but it has yet to be used in any pharmacological study. In the present study, we modified the OXA-induced colitis model in BALB/C mice to evaluate the efficacy of treatments for UC. Colitis was induced by intrarectal administration of OXA solution (7.5 mg/mL in 40% ethanol) in a BALB/C strain that is known to favor Th-2 immune responses. A lower mortality rate was obtained in the BALB/C strain than was found in the original method. Histological examination showed that there were morphological similarities to human UC. Increased mRNA expression of interleukin-13, a Th-2 cytokine, was observed in mesenteric lymph nodes. Intrarectal administration of 5-aminosalicylic acid or sodium prednisolone phosphate resulted in a significant improvement in the colitis. These results suggest that the OXA-induced colitis model in the BALB/C strain provides a new way to evaluate the efficacy of therapeutic agents for UC.
Kojima
Ryotaro
R
Research Laboratories, Nisshin Kyorin Pharmaceutical Co., Ltd., Iruma-gun, Saitama, Japan. kojimar@nk-pharm.co.jp
Kuroda
Satoko
S
Ohkishi
Tomiko
T
Nakamaru
Koichi
K
Hatakeyama
Shigeki
S
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000633:toxicity*; D011239:Prednisolone / Q000627:therapeutic use*
D010081:Oxazolone; D019804:Mesalamine; D011239:Prednisolone