Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model.

BACKGROUND & AIMS: Butyrate is effective in experimental colitis by increasing transglutaminase activity. Because ulcerative colitis increases the risk of colonic neoplasia, the aim of this study was to investigate whether butyrate treatment reduces mucosal sensitivity to colon cancer development in rats with experimental colitis.

METHODS

Colon cancer was induced by azoxymethane injections in 10 rats with trinitrobenzensulfonic acid-induced colitis and 10 rats without colitis. Three additional groups of rats with colitis were treated with butyrate, mesalamine, and saline enemas, respectively, twice daily for 8 weeks; 1 week after colitis induction, tumors were induced. Biopsy specimens for assessment of proliferation pattern and transglutaminase activity were obtained during the latent period of cancer development. Characteristics of tumors were recorded 27 weeks after the first exposure to azoxymethane.

RESULTS

Experimental colitis enhanced carcinogenesis; butyrate therapy reduced both incidence and size of tumors and also affected colonic proliferation pattern. Transglutaminase levels were restored by butyrate treatment in rats with colitis.

CONCLUSIONS

The protective effect of butyrate against large bowel cancer in experimental colitis suggests its usefulness in long-term therapy to decrease disease relapses and to reduce colon cancer risk in ulcerative colitis.