title: Chronic hypoxia alters glucose utilization during GSH-dependent detoxication in rat small intestine.
abstract: We showed that hypoxia alters glutathione (GSH)-dependent detoxication and induces mucosal metabolic instability. To determine the impact of these changes and the role of reductant supply in intestinal lipid peroxide disposition, pair-fed (16 g/day) Sprague-Dawley rats were exposed to air (20.9% O2; n = 6) or 10% O2 (n = 6) for 10 days. Jejunal and ileal everted sacs were exposed to 75 microM peroxidized fish oil with or without 10 mM glucose or 1 mM GSH. Peroxide transport was determined as the abluminal recovery of thiobarbituric acid-reactive substances. Peroxide recovery in hypoxic intestine was twice that in normoxic intestine. Addition of GSH and glucose did not affect peroxide recovery, indicating reduced intracellular GSH-dependent metabolism and enhanced output by the hypoxic intestine. Glucose uptake by normoxic and hypoxic intestine is similar, whereas its utilization for detoxication is decreased in hypoxic cells. Determination of NADPH supply indicates that decreased glucose availability for NADPH production during hypoxia impairs GSH disulfide reduction, compromises hydroperoxide metabolism, and increases peroxide output from hypoxic intestine.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: LeGrand
authors.forename: T Y
authors.initials: TY
authors.lastname: Aw
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D003958:Diamide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008054:Lipid Peroxides; D003958:Diamide; D009249:NADP; D005978:Glutathione; D005947:Glucose; D010100:Oxygen