Production of Mucosal Damage

Several studies have demonstrated the production of mucosal damage and/or increased mucosal permeability by hydrogen peroxide, the hydroxyl radical, or by installation of xanthine or glucose oxidase (Gregaard et al., 1982 Parks et al., 1984 Joubert-Smith et al., 1991 Kohen etal., 1992). 

Production of Mucosal Damage 2.3.1.2.1 Cell culture Stimulated neutrophils are known to be cytotoxic to cells in vitro (Dull et al., 1987 Dallegri et al., 1990 Grisham et al., 1990b). Several in vitro systems have been used to demonstrate oxidative damage to intestinal cells. Xanthine/XO increased Cr release and decreased [ H]thymidine uptake by IEC-18 small intestinal epithelial cell monolayers in a dose-dependent manner (Ma et al., 1991). Rat enterocytes show decreased trypan blue exclusion and increased protein release when incubated with neutrophils stimulated... 

Humans Hydrogen peroxide has been used as an enema or as a cleaning agent for endoscopes and may cause mucosal damage when applied to the surface of the gut wall. Hydrogen peroxide enteritis can mimic an acute ulcerative, ischaemic or pseudomembranous colitis, and ranges from a reversible, clinically inapparent process to an acute, toxic fulminant colitis associated with perforation and death (Bilotta and Waye, 1989). It is conceivable that anecdotal reports of exacerbation of IBD by iron supplementation (Kawai et al. 1992) are mediated by hydroxyl radical production by the Fenton reaction. 

Cysteinyl leukotrienes and platelet-activating factors released by eosinophils injure mucosal surfaces of the airways. Furthermore, they damage M2 muscarinic receptors and as a result the cholinergic response is unchecked in the absence of inhibitory M2 muscarinic receptors. The production of eosinophils is regulated... 

PGs produced in the gastric mucosa stimulate the secretion of both bicarbonate and the mucus gel to protect the mucosa from damage by gastric secretions. Use of NSAIDs, such as aspirin and ibuprofen, reduces the production of the prostanoids and so decreases the protection of the gastric mucosa, promoting mucosal erosion. 

A number of other mechanisms may contribute to the development of NSAID-induced mucosal injury. Neutrophil adherence may damage the vascular endothelium and may lead to a reduction in mucosal blood flow, or may liberate oxygen-derived free radicals and proteases. Leukotrienes, products of lipoxygenase metabolism, are inflammatory substances that may contribute to mucosal injury through stimulatory effects on neutrophil adherence (see Fig. 33-3). 

Most of the damage relating to the phenolic components in creosote and coal tar is immediate and requires no specific chronic management. It is recommended that mucosal surfaces be evaluated for possible scarring (especially the esophagus or cornea) if exposure was directly injurious. As with other ingested or inhaled PAHs (e.g., from combustion products like cigarette smoke), there are no documented means to enhance elimination of coal tars. 

Murakami M, Asagoe K, Dekigai H, et al. 1995. Products of neutrophil metabolism increase ammonia-induced gastric mucosal damage. Dig Dis Sci 40(2) 268-273. 

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