Oxidant-induced increases in mucosal permeability in developing piglets.
Reactive oxygen metabolites have been implicated in the pathogenesis of mucosal injury induced by ischemia-reperfusion in adult animals, with recent interest centering on the capacity of polymorphonuclear neutrophil-derived oxidants to mediate this injury. A role for oxidants has also been postulated in the etiology of neonatal necrotizing enterocolitis. Based on evidence that the intrinsic capacity of the neonatal piglet intestine to detoxify hydrogen peroxide (H2O2) is minimal relative to that of older piglets, we characterized the changes in mucosal permeability induced by luminal perfusion with H2O2 and hypochlorous acid at concentrations that can be produced physiologically by activated neutrophils (0.05 mmol/L, 0.1 mmol/L, and 0.5 mmol/L), in the distal ileum of 1-d- and 1-mo-old piglets. Mucosal permeability was quantitated by measurement of blood-to-lumen clearance of 51-labeled chromium EDTA. Luminal perfusion with either H2O2 (0.05 mmol/L and 0.1 mmol/L) or hypochlorous acid (0.1 mmol/L and 0.5 mmol/L) significantly increased mucosal permeability in newborn piglets but did not affect mucosal permeability in 1-mo-old animals. Perfusion with 0.5 mmol/L H2O2 significantly increased mucosal permeability over control values in both age groups, but injury in the newborn intestine was significantly greater than that observed in 1-mo-old animals. Thus, as predicted by the reduced intrinsic capacity of the mucosa of neonatal piglets to detoxify H2O2, the ileum of newborn piglets is more vulnerable to oxidant-induced mucosal injury than is the ileum of older animals.
Clark
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ES
Department of Physiology/Biophysics, Louisiana State University Medical Center, Shreveport 71130-3932.
Crissinger
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KD
Granger
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DN
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity*; D006997:Hypochlorous Acid / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D008297:Male; D010539:Permeability / Q000187:drug effects; D013552:Swine
D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide