Adaptive cytoprotection against acetic acid induced colonic injury in rats

Abstract

Background and aims: The phenomenon of prostaglandin dependent adaptive cytoprotection has been well established in the stomach and duodenum but not in the colon. This study investigated whether it also occurs in the colon. Methods: Fisher rats received intracolonic administration (0.5 ml) of saline or acetic acid at low concentrations (0.01–5%) followed by high concentration (25%) at various intervals (10–720 min). The distal colon was removed 2 h after acetic acid (25%), and colonic injury was assessed macroscopically and histologically and scored. Indomethacin (5 mg/kg) or N ^G-nitro-L-arginine methyl ester (10 mg/kg) was injected intraperitoneally 1 h or 30 min before pretreatment with 1% acetic acid. Results: Acetic acid (25%) administered into the colon induced 11.6±0.2 macroscopic scores and 10.0±0.4 histological scores in saline-pretreated rats, which were reduced to 0.3±0.2 and 1.8±0.5 by acetic acid (1%) pretreatment, respectively. The protective effect assessed macroscopically and histologically was dose related (0.01–1% acetic acid) and long lasting (maximal at 30 min and lasting up to 6 h). Indomethacin abolished the colonic adaptive cytoprotection while nitric oxide synthase inhibitor had no effect. Conclusions: These data show that prostaglandin dependent adaptive protection is induced by exposure of the colon to low concentrations of acetic acid, suggesting that endogenous defense mechanisms are increased in the colon by mild irritants.