Adaptive cytoprotection against acetic acid induced colonic injury in rats

Background and aims: The phenomenon of prostaglandin dependent adaptive cyt oprotection has been well established in the stomach and duodenum but not i n the colon. This study investigated whether it also occurs in the colon. M ethods: Fisher rats received intracolonic administration (0.5 ml) of saline or acetic acid at low concentrations (0.01-5%) followed by high concentrat ion (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-argin ine methyl ester (10 mg/kg) was injected intraperitoneally 1 h or 30 min be fore pretreatment with 1% acetic acid. Results: Acetic acid (25%) administe red into the colon induced 11.6+/-0.2 macroscopic scores and 10.0+/-0.4 his tological 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 protecti ve effect assessed macroscopically and histologically was dose related (0.0 1-1% 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 p rostaglandin dependent adaptive protection is induced by exposure of the co lon to low concentrations of acetic acid, suggesting that endogenous defens e mechanisms are increased in the colon by mild irritants.