Role of mucus in the repair of gastric epithelial damage in the rat. Inhibition of epithelial recovery by mucolytic agents.
A role for mucus in providing a microenvironment over sites of gastric damage, which is conducive to reepithelialization, has been proposed. We tested this hypothesis by examining the effects of disruption of such mucus on the recovery of epithelial integrity after damage induced by 50% ethanol. Exposure of an ex vivo chambered gastric mucosa to topically applied 50% ethanol resulted in copious release of mucus, cellular debris, and plasma, which formed a continuous cap over the mucosal surface. Ethanol-induced gastric damage was accompanied by extensive surface epithelial cell damage and a marked decrease in transmucosal potential difference. During the 30 min after ethanol was removed from the chamber, the epithelium became reestablished and the potential difference gradually recovered to 94% of the level before ethanol treatment. However, if the mucolytic agents N-acetylcysteine (5%) or pepsin (0.5%) were added to the bathing solutions, the "mucoid cap" disintegrated and the recovery of potential difference was significantly retarded (recovering to only 51% and 52% of levels before ethanol treatment). Histologic evaluation confirmed that mucosae treated with either agent had significantly less (p less than 0.005) intact epithelium at the end of the experiment. Removal of the mucoid cap with forceps caused a similar inhibition of the repair of the epithelium and the recovery of potential difference. Both mechanical and chemical (N-acetylcysteine) disruption of the mucoid cap resulted in a significant increase in the mucosal leakage of albumin and hemoglobin, supporting previous histologic evidence that the mucoid cap traps blood components over the damaged mucosa. These studies support the hypothesis that mucus released in response to topical application of an irritant plays an important role in the repair of epithelial damage through the process of restitution.
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009093:Mucus / Q000502:physiology*; D010434:Pepsin A / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D010434:Pepsin A; D000111:Acetylcysteine