Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport

The changes in short circuit current (electrogenic Cl^- secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H₂O₂, and the lack of effect of preincubation with deferoxamine or thiourea implicate H₂O₂, and not O₂^-• or OH^•, as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H₂O₂ stimulated colonic PGE₂ and PGE₂ production 8- and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic Cl secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. Cl^- secretion was reduced by cyclooxygenase inhibition. Also, the Cl^- secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H₂O₂ appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE₂, was blocked by tetrodotoxin. Therefore, PGI₂ may be the mediator of the H₂O₂ response. H₂O₂ produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport.