Interaction between oxygen radicals and gastric mucin

Abstract

The gastrointestinal epithelium is continuously exposed to reactive oxygen metabolites that are generated within the lumen. In spite of this exposure, the healthy epithelium appears unaffected, suggesting efficient mechanisms for protection against these potentially cytotoxic oxidants. The objective of this study is to characterize the interaction between purified gastric mucin and hydroxyl radicals generated from the interaction between ferric iron and ascorbic acid. We found that both native and pronase-treated mucin effectively scavenged hydroxyl radical and that the scavenging properties were not significantly different. The effective concentration of mucin required for a 50% reduction in malondialdehyde production was approximately 10 mg/ml for both native and pronase-treated mucin. In addition, the iron-ascorbic system produced a dramatic decrease (greater than 50%) in the specific viscosity of mucin that was inhibited by catalase, deferoxamine, and mannitol. Superoxide dismutase had no effect. These data suggest that hydroxyl radicals derived from the iron-catalyzed decomposition of hydrogen peroxide are responsible for the depolymerization of native mucin. We propose that mucin may provide protection to the surface epithelium of the gastrointestinal tract by scavenging oxidants produced within the lumen; however, it does so at the expense of its viscoelastic properties.

Oxygen radicals in ulcerative colitis

“…Kim and Byrd [75] have proposed that defects in mucin synthesis or enhanced mucin degradation may be important in the pathophysiology of ulcerative colitis. Grisham and co-workers have recently shown that hydroxyl radical degrades and depolymerizes purified mucin, as measured by decreases in viscosity [76]. Thus, if one considers mucin depletion as the result of increased oxidative stress, perhaps along the biochemical lines studied by Baker and co-workers [77] for the degradation of articular cartilage proteoglycan, the mucin defect theory and the oxygen radical theory become unified.…”

Interactions of oxygen radicals with airway epithelium.

“…Mucus also is known to have antioxidant capabilities (44). The sugar moieties in mucus may act similarly to mannitol and glucose in scavenging hydroxyl radical and H202 (45,46). Mucus glycoproteins react with H202; in the process both H202 and glycoproteins are degraded (44,47,48 (52), increased nonspecific airway reactivity, increased specific airway resistance, increased respiratory frequency on exercise, and an involuntary reduction of maximal inspiratory capacity (53).…”

Protective Effect of Teprenone Against Acute Gastric Mucosal Lesions Induced by Compound 48/80, a Mast Cell Degranulator, in Rats

“…It is known that gastric mucin interacts with ROS, especially hydroxyl radical in vitro (17). We have reported that teprenone exerts protective and preventive effects against acute gastric mucosal lesions in rats with water immersion restraint stress not only by preservation of gastric mucus synthesis and secretion but also by inhibition of neutrophil infiltration and enhanced lipid peroxidation in the gastric mucosa (13).…”