Butyric acid is a physiological component of the colonic environment that possesses anti-inflammatory and antitumor properties, among others. However, little is known regarding its effects following direct application on the colonic surface. This study was conducted to investigate the topical anti-inflammatory effect of calcium butyrate in chemically-induced colitis in rats and to evaluate its antitumor properties in vivo and in vitro. The anti-inflammatory activity of calcium butyrate was evaluated in dinitrobenzene sulfonic acid-induced colitis in rats, following intracolonic instillation for 6 consecutive days and its in vivo antitumor activity was evaluated in F344 rats with the azoxymethane (AOM)-induced aberrant crypt foci (AFC) test, following intracolonic instillation for 4 weeks. The in vitro antiproliferative activity was assessed by incubation for 48 h with the HT29, SW620 and HCT116 intestinal tumour cell lines to evaluate the rate of 3H-thymidine uptake. In dinitrobenzene-induced colitis, the intracolonic instillation of calcium butyrate completely prevented body weight reduction in the animals and counteracted the local noxious effects of the irritant by reducing colon edema (-22.7%, P=0.048) and the area of mucosal damage (-48%, P=0.045). In the AOM-induced AFC test, the intracolonic instillation of calcium butyrate significantly reduced the number of AFC in the entire colon (-22.7%, P<0.05). Calcium butyrate, following incubation with the HT29, SW620 and HCT116 tumour cell lines, induced a significant antiproliferative, dose-dependent effect (P=0.046 to P=0.002) in all three strains, as measured by the reduction in 3H-thymidine uptake. Calcium butyrate directly applied to the mucosa of the rat colon was able to ameliorate colonic inflammation, suggesting a possible beneficial role in the treatment of inflammatory colon diseases. Moreover, calcium butyrate exhibited notable antitumor effects in vivo and in vitro; however, their clinical relevance requires confirmation by additional clinical investigations.
Keywords: calcium butyrate; colorectal cancer; experimental colitis; inflammatory bowel disease; short-chain fatty acids.