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T Y Aw

Publications and source records attributed to T Y Aw.

At least 37 records · Page 2Linked to original sources
PubMed1997

Luminal peroxides in intestinal thiol-disulfide balance and cell turnover.

Dietary intake of highly polyunsaturated fats represents a major source of lipid hydroperoxides in the intestinal lumen. Under conditions of high peroxide intake, excessive concentrations of lipid hydroperoxides can persist in the gut lumen and contribute to impairment of mucosal GSH-dependent detoxication pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, including cancer. This paper summarizes our current knowledge of the determinants of intestinal lipid hydroperoxide metabolism and of the physiological and biochemical processes in lipid peroxide-mediated changes in intestinal redox status, regulation of mucosal thiol and antioxidant balance and control of intestinal cell turnover. This discussion is pertinent to understanding dietary peroxides and thiol redox balance in intestinal physiology and pathophysiology and the potential benefit of oral GSH in preserving metabolic integrity of the intestinal epithelium.

Animals↗
PubMed1997

Chronic hypoxia, glutathione-dependent detoxication, and metabolic instability in rat small intestine.

We previously showed that chronic hypoxia decreases activity of intestinal glutathione (GSH)-dependent enzymes and is associated with a proximal-to-distal gradient of enzyme activity, suggesting reduced detoxication capacity in ileal cells. To assess whether hypoxia affects metabolism of hydroperoxides, jejunal and ileal enterocytes from rats exposed to air (n = 11) or 10% O2 (n = 9) for 10 days were exposed to 300 microM tert-butyl hydroperoxide (t-BH). The initial rate of hydroperoxide metabolism was 50-90% faster in hypoxic enterocytes, but cell killing was enhanced. Metabolism in normoxic, but not hypoxic, cells was enhanced threefold by addition of 10 mM glucose. Hypoxic enterocytes exhibited a higher baseline GSH/GSH disulfide (GSSG) ratio but a larger percent decrease after t-BH exposure. t-BH induced a 35-40% decrease in protein-bound sulfhydryl groups in normoxic and hypoxic enterocytes, but protein-bound sulfhydryl was protected by glucose in normoxic cells only. Metabolic response to substrate load or hydroperoxide challenge was assessed by measurement of cellular O2 consumption. Hypoxia, but not normoxia, increases and decreases O2 consumption on exposure to glucose and oxidant, respectively, suggesting metabolic dysregulation. In summary, prolonged O2 deficiency induces loss of intestinal metabolic integrity that is associated with altered peroxide detoxication activity and mitochondrial respiratory function.

Animals↗
PubMed1997

Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells.

Oxidants generated by endothelial xanthine oxidase (XO) can help trigger free radical-mediated tissue injury. An important event in oxidant-mediated tissue injury is neutrophil-endothelial adhesion. Although activation of endothelial XO increases adhesion, little is known about xanthine in the adhesive effect of XO. This study examined administered xanthine on the adhesion of neutrophils. Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were exposed to xanthine (15 min), and neutrophils were allowed to adhere to HUVEC in an adhesion assay. Adhesion was dose dependently increased by xanthine (3-100 microM). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 microM), or platelet-activating factor (PAF) receptor antagonist (WEB 2086; 10 microM) reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect. Pretreatment of HUVEC with 50 microM tungsten also blocked xanthine-induced adherence. Adhesion was also inhibited by preincubation with 100 U/ml heparin. Finally, anti-P-selectin antibody (PB1.3; 20 micrograms/ml) attenuated adhesion. Our results indicate that xanthine may promote neutrophil-endothelial adhesion via a hydrogen peroxide- and PAF-mediated P-selectin expression.

Antioxidants↗
PubMed1997

Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells.

The objectives of this study were to (1) determine the time course of neutrophil adhesion to monolayers of human umbilical vein endothelial cells (HUVECs) that were exposed to 60 minutes of anoxia followed by 30 to 600 minutes of reoxygenation and (2) define the mechanisms responsible for both the early (minutes) and late (hours) hyperadhesivity of postanoxic HUVECs to human neutrophils. The results clearly demonstrate that anoxia/reoxygenation (A/R) leads to a biphasic increase in neutrophil adhesion to HUVECs, with peak responses occurring at 30 minutes (phase 1) and 240 minutes (phase 2) after reoxygenation. Oxypurinol and catalase inhibited phase-1 adhesion, suggesting a role for xanthine oxidase and H2O2. In comparison, platelet activating factor (PAF) contributed to both phases of neutrophil adhesion. Anti-intercellular adhesion molecule-1 (ICAM-1) and anti-P-selectin antibodies (monoclonal antibodies [mAbs]) attenuated phase-1 neutrophil adhesion, consistent with roles for constitutively expressed ICAM-1 and enhanced surface expression of preformed P-selectin. Phase-2 neutrophil adhesion was attenuated by an anti-E-selectin mAb, indicating a dominant role of this adhesion molecule in the late phase response. Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides containing the nuclear factor-kappa B or activator protein-1 cognate DNA sequences significantly attenuated phase-2 response, suggesting a role for de novo macromolecule synthesis. Surface expression of ICAM-1, P-selectin, and E-selectin on HUVECs correlated with the phase-1 and -2 neutrophil adhesion responses. Collectively, these findings indicate that A/R elicits a two-phase neutrophil-endothelial cell adhesion response that involves transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules.

Azepines↗
PubMed1996

Chronic hypoxia and glutathione-dependent detoxication in rat small intestine.

It has previously been found that chronic O2 deficiency decreases activity of the enzymes of the glutathione (GSH) redox system in the liver. To study the effects of O2 deficiency on intestinal detoxication capacity, pair-fed (16 g food/day) Sprague-Dawley rats were exposed to air (20.9% O2; n = 4) or 10% O2 (n = 4) for 10 days. Animals were killed, and intestinal mucosal homogenate (20% wt/vol) was obtained and assayed for activities of glucose-6-phosphate dehydrogenase (G6PD), GSH peroxidase (GSHPx), GSH disulfide reductase (GSSGRd), and gamma-glutamyl cysteine synthetase (gamma-GCS). Hypoxia decreases activities of GSHPx, GSSGRd, and gamma-GCS by approximately 50%, which suggests compromised detoxication. A proximal-to-distal reduction in enzymatic capacity indicates impairment of detoxication may be more pronounced in the distal intestine. G6PD, a key enzyme in NADPH production, remains unchanged. Urinary malondialdehyde was also monitored. Hypoxic rats exhibited a threefold increase in thiobarbituric acid-reactive substance, consistent with a generalized oxidative stress in these animals. Taken together, the results indicate that chronic hypoxia promotes tissue oxidative stress and impairs the ability of the enterocyte to metabolize ingested oxidants.

Animals↗
PubMed1995

Determinants of hydroperoxide detoxification in diabetic rat intestine: effect of insulin and fasting on the glutathione redox cycle.

The capacity for hydroperoxide detoxification in diabetic (DM) intestine was studied in streptozocin-induced DM rats by quantification of the intestinal glutathione (GSH) redox cycle, a key cellular pathway for peroxide elimination. A role for luminal glucose in regulation of redox cycle activity was examined in insulin-treated or 24-hour-fasted DM animals. Intestinal activities of the redox enzymes, GSH peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase (G6PD), were significantly decreased by 17 hours' insulin treatment, whereas only G6PD was decreased by fasting. Mucosal GSH levels were also markedly decreased under these conditions. These results are consistent with an overall suppression of intestinal GSH redox cycle function by short-term administration of insulin. Insulin treatment for 7 consecutive days increased hepatic G6PD activity by fourfold but was without effect on intestinal G6PD, suggesting tissue specificity in insulin regulation of G6PD. The rate of metabolism of tert-butyl hydroperoxide (tBH) in isolated enterocytes was low in the absence of substrates (0.51 +/- 0.07 nmol/10(6) cells/min) but was increased fivefold by exogenous glucose (2.70 +/- 0.11 nmol/10(6) cells/min), indicating that glucose availability is an important contributor to intestinal detoxification of toxic hydroperoxides. Collectively, the current results show that GSH redox cycle enzymes in DM intestine are under coordinate insulin control, and that this control appears to be downregulated by short-term insulin treatment.

Animals↗
PubMed1995

Enterocyte respiration rates in feline small intestine exposed to graded ischemia.

The purpose of our study was to investigate the changes in enterocyte cellular and mitochondrial respiration rates subsequent to ischemia of graded duration. The small intestine of anesthetized adult cats was assigned to one of five treatment regimens: control or ischemia of 15-, 30-, 60-, or 90-min duration. Cellular and mitochondrial respiration was measured using a Clark-type O2 electrode at 0 and 4 h postharvest. Ischemia of increasing duration caused a progressive decrease in cellular and mitochondrial respiration in enterocytes at 0 h postharvest. By 4 h postharvest, cellular and mitochondrial respiration rates for the 15-, 30-, and 60-min ischemic groups had recovered to near control levels, whereas the 90-min group showed minimal recovery. These data suggest that ischemia suppresses cellular and mitochondrial respiration of intestinal epithelial cells, the magnitude of which is related to the ischemic duration. The ischemia-induced suppression in cellular respiration primarily reflects a reduction in mitochondrial respiration.

Animals↗
PubMed1995

Mechanisms of oxidized chylomicron-induced leukocyte-endothelial cell adhesion.

The objectives of this study were to determine whether oxidatively modified chylomicrons (oxCM) can elicit leukocyte-endothelial cell adhesion in the mesenteric microcirculation and to define the mechanisms underlying the oxCM-induced adhesive interactions. Oxidation of chylomicrons (CM) with the peroxyl radical generator 2,2'-azobis(2-amidinopropane)hydrochloride was associated with the formation of thiobarbituric acid-reactive substances and lipid hydroperoxides. Leukocyte rolling, adherence, and emigration as well as erythrocyte velocity were monitored in rat mesenteric venules infused with either native CM or oxCM. oxCM, but not native CM, increased the numbers of rolling, adherent, and emigrated leukocytes. The oxCM-induced leukocyte adherence was significantly blunted by pretreating the animals with either superoxide dismutase, a platelet-activating factor (PAF) receptor antagonist, or monoclonal antibodies (MAb) directed against either CD11/CD18 or intracellular adhesion molecule 1. A MAb against P-selectin reduced oxCM-induced leukocyte rolling but not adherence. These findings suggest that the increased plasma oxCM levels associated with ingestion of oxidized lipids may promote leukocyte adhesion through a mechanism that involves the superoxide anion, PAF, and adhesion receptors on leukocytes and endothelial cells.

Animals↗
PubMed1995

Oxidized LDL-induced microvascular dysfunction. Dependence on oxidation procedure.

Human LDLs oxidized with Cu2+ are known to promote leukocyte-endothelial cell adhesion (LECA) and albumin leakage in postcapillary venules. The objective of this study was to compare the ability of LDL oxidized with Cu2+ (Cu-LDL), phospholipase A2 plus lipoxygenase (PLA2-LDL), horseradish peroxidase plus H2O2 (HRP-LDL), or -OCl (-OCl-LDL) to promote (1)neutrophil-endothelial cell adhesion (NECA) in vitro and (2)LECA and albumin leakage in rat mesenteric venules. In vitro adhesion assays revealed that only Cu-LDL elicited a dose-dependent NECA response, whereas PLA2-LDL but not normal (N-LDL), HRP-LDL, or -OCl-LDL increased NECA at the highest concentration studied (670 micrograms/mL). The magnitude of the NECA responses elicited by the different forms of oxidized LDL was related to the degree of lipid peroxidation but unrelated to the level of protein oxidation. Local intra-arterial infusion of Cu-LDL, PLA2-LDL, or -OCl-LDL but not N-LDL elicited significant increases in leukocyte adherence and emigration, mast cell degranulation, and albumin leakage in rat mesenteric venules. The LECA induced by all forms of oxidized LDL was not accompanied by significant alterations of venular shear rate.

Animals↗
PubMed1995

Microvascular responses to inhibition of nitric oxide production. Role of active oxidants.

The objective of this study was to assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte-endothelial cell adhesion and increased microvascular permeability observed in rat mesenteric venules after inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration and leakage of fluorescein isothiocyanate-labeled albumin were monitored in postcapillary venules before and after exposure of the tissue to L-NAME. H2O2 production in mesenteric tissue was monitored by using dihydrorhodamine 123 (DHR), the H2O2-sensitive fluorochrome. L-NAME elicited a rapid increase in both the rate of albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules. Treatment with either catalase or dimethylthiourea attenuated the L-NAME-induced oxidative stress, albumin leakage, and leukocyte-endothelial cell adhesion. Oxidation of DHR was enhanced in animals treated with either 3-amino-1,2,4-triazole (ATZ), an inhibitor of endogenous catalase, or a combination of ATZ and maleic acid diethyl ester, which depletes intracellular glutathione. Animals receiving a CD11/CD18-specific antibody to prevent leukocyte adhesion/emigration exhibited a reduced oxidation of DHR in response to L-NAME. These findings indicate that most of the H2O2 (and secondarily derived oxidants) generated in mesenteric tissue exposed to an inhibitor of nitric oxide production is due to accumulation of activated leukocytes.

Amino Acid Oxidoreductases↗
PubMed1994

Omega 3-lipid peroxides injure CaCo-2 cells: relationship to the development of reduced glutathione antioxidant systems.

BACKGROUND/AIMS: Dietary polyunsaturated fats are significant sources of luminal lipid hydroperoxides whose accumulation can be injurious to the intestinal epithelium. The current study examines the cytotoxicity of peroxidized fish oil to CaCo-2 cells. METHODS: Chromate release from cells was used as an index of CaCo-2 injury, and day 1 and day 7 postconfluent monolayers were used to represent the immature and mature states, respectively. RESULTS: Air oxidation of fish oil yielded equimolar quantities of hydroperoxyeicosapentaenoic (20:5) and docosahexaenoic (22:6) acids. Their cytotoxicity were time- and concentration-dependent and were related to the developmental stages. A 100-mumol/L dose of hydroperoxides caused a 40% and a 15% 51Cr release from day 1 and day 7 cells, respectively. Cellular glutathione (GSH), GSH redox enzyme, and gamma-glutamyl cysteine synthetase activities were significantly lower in day 1 than in day 7 cells, indicating that hydroperoxide metabolism in immature cells is rate limited by reductant supply. GSH supplementation increased cell GSH in day 7 cells (twofold) but not in day 1 cells, suggesting a limited ability of immature cells to use exogenous GSH. CONCLUSIONS: These results show that nondifferentiated cells are more sensitive to oxidant-induced injury than mature cells. This enhanced susceptibility is associated with a lower GSH-dependent detoxication capacity of the immature cells.

Antioxidants↗
PubMed1994

Biliary glutathione promotes the mucosal metabolism of luminal peroxidized lipids by rat small intestine in vivo.

We previously found that exogenous GSH enhances mucosal GSH and promotes lipid hydroperoxide metabolism by rat small intestine (AW, T. Y., and M. W. WIlliams, 1992. Am. J. Physiol. 263:G665-G672). In this study, we have developed an in vivo bile and lymph fistula rat model to test the hypothesis that biliary GSH is an important luminal source of GSH. Peroxidized fish oil was infused into the proximal intestine, and hydroperoxide accumulation in lumen, mucosa, and lymph was determined. Diversion of bile decreased mucosal GSH and increased hydroperoxide accumulation in all fractions. Supplementation with GSH, but not with GSSG, increased tissue GSH and attenuated hydroperoxide accumulation (50-60%), consistent with enhancement of hydroperoxide removal by exogenous GSH. Addition of native bile deficient in GSH, but not cysteine, cystine, or GSSG, decreased luminal and lymph hydroperoxide levels by 20-30%. Amino acid supplementation concurrently attenuated hydroperoxide recoveries in these fractions by 30-40% and increased mucosal GSH by 40%, indicating a role for biliary amino acids in hydroperoxide elimination. The effect of amino acids was abolished by buthionine sulfoximine, confirming their role in GSH biosynthesis. Collectively, the results demonstrate that bile is a rich source of reductant for maintaining mucosal GSH to promote intestinal metabolism of luminal peroxidized lipids.

Analysis of Variance↗
PubMed1994

Development of ischemia/reperfusion tolerance in the rat small intestine. An epithelium-independent event.

In stable organ systems, such as the heart and kidneys, an oxidant stress induces an increase in endogenous antioxidant systems resulting in an increased resistance of the tissue to a subsequent oxidant challenge. The development of this oxidant tolerance requires 1.5-6 d. The aim of the present study was to determine whether oxidant tolerance can be induced in the small intestinal mucosa, a labile system whose epithelium turns over every 2-3 d. Ischemia/reperfusion-induced epithelial barrier dysfunction of the small intestinal mucosa was monitored in Sprague-Dawley rats whose intestines had been exposed to an ischemic insult 1, 24, or 72 h previously. At 24 h, but not 1 or 72 h after the initial ischemic insult, the mucosa was more resistant to ischemia/reperfusion-induced barrier dysfunction. The antioxidant status of the mucosa was enhanced at 24 h, but not at 1 or 72 h after the initial ischemic insult. This adaptation appears to be specific for oxidants, since an initial ischemic insult imposed 24 h earlier also protected against H2O2-induced, but not acid- or ethanol-induced, barrier dysfunction. Further studies indicated that the increase in antioxidant status of the mucosa observed 24 h after the initial ischemic insult was a result of adaptational changes in the lamina propria, rather than the epithelium. In vitro studies with isolated epithelial cells also indicated that epithelial cells do not develop oxidant tolerance. We conclude that the development of oxidant tolerance in the small intestinal mucosa does not involve an active participation of the epithelial lining.

Animals↗
PubMed1994

Glucose regulation of hydroperoxide metabolism in rat intestinal cells. Stimulation of reduced nicotinamide adenine dinucleotide phosphate supply.

The regulation of intestinal metabolism of t-butylhydroperoxide by glucose was examined in isolated enterocytes from proximal rat intestine. The basal rate of hydroperoxide elimination in control cells was 0.57 +/- 0.05 nmol/min per 10(6) cells, and was increased threefold by 10 mM exogenous glucose (1.74 +/- 0.14 nmol/min per 10(6) cells). Concurrently, cellular NADPH levels increased threefold (1.62 +/- 0.40 nmol/10(6) cells vs 0.57 +/- 0.14 nmol/10(6) cells in controls). The glucose effect was blocked by 6-aminonicotinamide and by 1,3-bis-(2-chloroethyl) 1-nitrosourea, consistent with glucose stimulation of NADPH production by the pentose phosphate shunt, and of NADPH utilization for glutathione disulfide reduction. The NADPH supply rate was quantified by controlled infusions of diamide, a thiol oxidant. At diamide infusion of 0.05 nmol/min per 10(6) cells, GSH and protein thiols in control cells were decreased significantly, consistent with a limited capacity for glutathione disulfide reduction. With glucose, cell GSH and protein thiols were preserved at a 10-fold higher diamide infusion which was reversed by 6-aminonicotinamide, supporting the view that glucose promotes glutathione disulfide reduction by increased NADPH supply. Collectively, the results demonstrate that intestinal metabolism of hydroperoxides subscribes to regulation by glucose availability. This responsiveness to glucose suggests that nutrient availability would be an important contributing factor in the detoxication of toxic hydroperoxides by the small intestine.

6-Aminonicotinamide↗
PubMed1992

Effect of chronic hypoxia on detoxication enzymes in rat liver.

Studies were performed to determine the effects of chronic hypoxia on enzymes that catalyze various detoxication reactions. Rats were exposed to room air or 10.5% O2 for 10 days, and microsomes and postmicrosomal supernatants were isolated from liver. Detoxication enzyme activities were measured by radiochemical and spectrophotometric assays, and immunoreactive protein amounts were measured by Western blot analysis. Total cytochrome P450, as measured by the CO-difference spectrum, and activities of superoxide dismutase (EC 1.15.1.1), epoxide hydrolase (EC 4.2.1.63), catalase (EC 1.11.1.6), glutathione disulfide reductase (EC 1.6.4.2), and glutathione (GSH) S-transferase (EC 2.5.1.18) were not affected by this extent of hypoxia. In contrast, 10 days of hypoxia decreased activities or immunoreactivities (% of aerobic) of GSH peroxidase (EC 1.11.1.9) (54%), cytochrome P450EtOH2 (42%), CYP3A1 (53%), sulfotransferase (EC 2.8.2.1) (77%) and UDP-glucuronosyltransferase (EC 2.4.1.17) (65%). Activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), an important enzyme in NADPH production was also decreased to 56% of the aerobic value, but Western blot analysis showed that the amount of protein reactive with antibodies to glucose-6-phosphate dehydrogenase was not affected by hypoxia. Thus, hypoxia may decrease activity of enzymes by regulatory mechanisms even though the amount of immuno-detectable enzyme is unchanged. Liver cells isolated from rats exposed to hypoxia also gave lower GSH synthetic rates than cells from normoxic rats. This result, together with the effect of hypoxia on glucose-6-phosphate dehydrogenase, indicates that the GSH supply for GSH-dependent detoxication reactions may be limited due to chronic hypoxia. To test directly whether chronic hypoxia increased sensitivity to a compound normally detoxified by a GSH-dependent reaction, sensitivity to tert-butyl hydroperoxide (t-BuOOH) of hepatocytes from rats exposed to in vivo hypoxia was compared to that from normoxic rats. The results showed that the cells from the hypoxic rats were much more sensitive to injury. Taken together, these results suggest that decreases in amounts and/or activities of detoxication enzymes during chronic hypoxia may result in increased susceptibility of cells to chemical injury.

Animals↗
PubMed1992

Postanoxic oxidative injury in rat hepatocytes: lactate-dependent protection against tert-butylhydroperoxide.

Previous studies in this laboratory showed that hypoxia and anoxia enhance the susceptibility of hepatocytes to tert-butylhydroperoxide (TBH)-induced oxidative injury. To determine whether preceding exposure to anoxia affects postanoxic sensitivity to oxidative injury, viability was studied in hepatocytes incubated under anoxic conditions followed by reoxygenation without or with tert-butylhydroperoxide addition. Results showed that a preceding exposure to 60 min of anoxia substantially increased the vulnerability of cells to injury by the oxidant. Because substantial tissue lactate can accumulate during anoxia, the effect of increased lactate on postanoxic injury due to TBH was determined. Results showed that added lactate protected in a concentration-dependent manner. The TBH elimination rate was stimulated by lactate, and the pyruvate production rate approached the rate of TBH elimination. Thus, lactate protects against postanoxic oxidative injury by supplying reducing equivalents for peroxide reduction. This suggests that lactate accumulation during ischemia may be beneficial and that supplementation with lactate could be considered as a means to protect against postischemic injury.

Animals↗
PubMed1992

Absorption and lymphatic transport of peroxidized lipids by rat small intestine in vivo: role of mucosal GSH.

The absorption and lymphatic transport of peroxidized MaxEPA fish oil was studied using the lymph fistula rat to determine the role of mucosal glutathione (GSH) in intestinal metabolism of luminal lipid hydroperoxides. Decreasing intestinal GSH concentrations with buthionine sulfoximine (BSO, 1.15 +/- 0.20 nmol/g), diethyl maleate (DEM, 0.93 +/- 0.26 nmol/g), phorone (1.46 +/- 0.14 nmol/g), or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, 1.54 +/- 0.18 nmol/g) compared with control (2.60 +/- 0.38 nmol/g) resulted in higher luminal recovery of the infused lipid hydroperoxide (% of infused dose): BSO (87.8 +/- 4.8%), DEM (86.1 +/- 1.3%), phorone (78.1 +/- 2.1%), and BCNU (71.7 +/- 4.8%) compared with control (52.8 +/- 4.3%). These results suggest that decreased elimination of luminal peroxidized lipids is associated with decreased tissue GSH. Treatment of rats with BSO, DEM, phorone, or BCNU resulted in dramatic increases in appearance of peroxidized lipids in lymph over 6-h lipid infusion (54.7 +/- 3.7, 57.7 +/- 4.6, 46.4 +/- 2.7, and 42.1 +/- 3.9 nmol, respectively) compared with control (20.5 +/- 3.4 nmol). The results are consistent with decreased intracellular metabolism of absorbed hydroperoxides and enhanced transport into lymph under GSH-deficient conditions. The current findings suggest that the function of the mucosal GSH peroxidase/oxidized glutathione (GSSG) reductase system may play an important role in intestinal handling of luminal lipid hydroperoxides. A compromised function of this detoxication mechanism in GSH-deficient states can significantly alter the metabolic fate of dietary peroxidized lipids.

Absorption↗