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Biomedical subjects

B Frei

Publications and source records attributed to B Frei.

At least 73 records · Page 4Linked to original sources
PubMed1996

Ascorbic acid and atherosclerotic cardiovascular disease.

In this chapter, we have briefly reviewed the current scientific knowledge of the role of vitamin C in the prevention of atherosclerosis and its associated clinical manifestations. There is good evidence from animal studies that vitamin C can slow the progression of experimental atherosclerosis. Most of these studies, however, were done either in guinea pigs, using ascorbic acid depletion, or in cholesterol-fed rabbits, using ascorbic acid supplementation. Both animal models have limitations, as guinea pigs are not a well-established (nor well-studied) model of atherosclerosis, and rabbits develop atherosclerosis at high serum beta-VLDL cholesterol levels, and in addition can synthesize ascorbic acid. In contrast, humans develop atherosclerosis spontaneously and readily at moderately elevated serum LDL cholesterol levels and have lost the ability to synthesize ascorbic acid. Thus, the animal studies discussed, although quite promising and suggestive of an anti-atherogenic effect of ascorbic acid, need to be expanded to primates before more definitive conclusions can be drawn. Similar to the animal data, the current evidence from epidemiological studies on the role of vitamin C in the prevention of CVD is inconclusive, with some studies showing a very strong correlation between increased vitamin C intake and incidence of CVD events and other studies showing no correlation at all. Studies on CVD risk factors indicate that vitamin C may moderately decrease total serum cholesterol levels, increase HDL levels, and exert a hypotensive effect. These findings are particularly intriguing and should be pursued vigorously in basic research studies to elucidate biological mechanisms. In addition, it appears that large placebo-controlled, double-blind, randomized trials of vitamin C supplementation (without simultaneous supplementation with vitamin E) in populations with a wide range of vitamin C body levels are needed in order to confirm or refute a role for vitamin C in the prevention of CVD. Unfortunately, no such trials are currently being conducted. The possible mechanisms by which ascorbic acid may affect the development of atherosclerosis and the onset of acute coronary events include effects on arterial wall integrity related to biosynthesis of collagen and GAGs, altered cholesterol metabolism mediated by vitamin C-dependent conversion of cholesterol to bile acids, and effects on triglyceride levels via modulation of lipoprotein lipase activity. A particularly intriguing possible mechanism for the anti-atherogenic effect of vitamin C is prevention of atherogenic, oxidative modification of LDL. Numerous in vitro studies have demonstrated that ascorbic acid strongly inhibits LDL oxidation by a variety of mechanisms. The potential effects of ascorbic acid on platelet function and EDRF metabolism are particularly intriguing, as they might have widespread consequences for the prevention of atherosclerotic lesion development as well as acute clinical events. Thus, both metabolic and antioxidant functions may contribute to the possible reduction of CVD risk by vitamin C.

Animals↗
PubMed1996

Antibacterial hydroperoxysterols from Xanthosoma robustum.

Three new hydroperoxysterols, 24-hydroperoxy-4 alpha, 14 alpha- dimethylcholesta-8,25-dien-3 beta-ol, 25-hydroperoxy-4 alpha, 14 alpha-dimethylcholesta-8,23-dien-3 beta-ol and 25-hydroperoxycycloart-23-en- 3 beta-ol, have been isolated from the aerial parts of Xanthosoma robustum, besides 24-hydroperoxycycloart-25-en-3 beta-ol, 4 alpha, 14 alpha-dimethylcholesta-8,24-dien-3 beta-ol and cycloartenol. Additionally, the two new diols, 4 alpha, 14 alpha-dimethylcholesta-8,25-dien-3 beta, 24-diol and 4 alpha, 14 alpha-dimethylcholesta-8,23-dien-3 beta, 25-diol were obtained from the first two hydroperoxysterols, respectively, by reduction with triphenylphosphine. The structures have been defined by chemical and spectroscopic studies. The four hydroperoxysterols exhibited antibacterial activities against Escherichia coli, Bacillus subtilis and Micrococcus luteus.

Anti-Bacterial Agents↗
PubMed1996

Mechanisms of metal ion-dependent oxidation of human low density lipoprotein.

Although either copper or iron is essential for oxidation of human low density lipoprotein (LDL) by vascular cells, the mechanism is unknown. In our experiments copper- and iron-mediated LDL oxidation was found to proceed by different mechanisms. Oxidation of LDL by iron requires superoxide and proceeds by a hydroxyl radical-independent mechanism involving reduction of iron from the ferric to the ferrous form. In contrast, copper-mediated LDL oxidation involves direct reduction of copper from the cupric to the cuprous form by LDL.

Copper↗
PubMed1996

Basic research in antioxidant inhibition of steps in atherogenesis.

Oxidised low-density lipoprotein (LDL) contributes to atherogenesis by a number of mechanisms, and antioxidants may act as anti-atherogens. LDL oxidation is inhibited by LDL-associated antioxidants, particularly alpha-tocopherol (vitamin E), and water-soluble antioxidants present in LDL's biologic milieu, especially ascorbate (vitamin C). In addition to protecting LDL against oxidation, antioxidants may act at the level of the vascular cell by limiting cellular production of reactive oxygen species, and, thus, cell-mediated LDL oxidation. Cellular antioxidants can also protect against vascular cell dysfunction that would otherwise promote atherogenesis, such as increased adhesion molecule expression and monocyte recruitment, impaired production or release of nitric oxide, or both, and the proliferation of smooth muscle cells. Some of these processes are regulated by nuclear factor-kappa B or related transcription factors, which are redox-sensitive and inhibited by antioxidants. Furthermore, cellular antioxidants can limit cytotoxic effects of oxidised LDL and other oxidant insults, inhibiting vascular cell necrosis and lesion progression. Finally, some antioxidants, in particular alpha-tocopherol, may affect atherogenesis by inhibiting platelet function and mural thrombosis, although this effect appears to be explained by the inhibition of protein kinase C independent of alpha-tocopherol's antioxidant activity.

Animals↗
PubMed1995

Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein.

Lipid peroxidation and oxidative modification of low-density lipoprotein (LDL) have been implicated as causal factors in the pathogenesis of atherosclerosis, and prevention of LDL oxidation by antioxidants may be an effective strategy to inhibit the progression of the disease. We investigated the effects of the reduced form of vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product (dehydro-L-ascorbic acid, DHA) upon metal ion-dependent oxidative modification of human LDL. We found that low micromolar concentrations of both AA and DHA protect LDL against oxidation induced by Cu2+ or by hemin and hydrogen peroxide. In a dose-dependent manner, AA and DHA prevented the initiation of lipid peroxidation in LDL, as determined by a sensitive and selective assay for lipid hydroperoxides utilizing HPLC with chemiluminescence detection. AA and DHA also preserved the LDL-associated antioxidants alpha-tocopherol, beta-carotene, and lycopene, but not ubiquinol-10. Furthermore, AA was able to stop propagation of lipid peroxidation in LDL, whereas DHA lacked this ability. The addition of 60 microM AA to LDL containing up to 38 nmol/mg protein of pre-formed lipid hydroperoxides led to their rapid disappearance; this activity of AA was dependent on the presence of redox-active copper, but did not lead to the formation of lipid hydroxides, the reduced form of lipid hydroperoxides. Our data show that in Cu(2+)-exposed LDL (i) vitamin C primarily spares, rather than regenerates, alpha-tocopherol and other endogenous antioxidants, except for AA and DHA prevent initiation of lipid peroxidation in LDL; and (iii) AA can terminate lipid peroxidation, thereby protecting partially oxidized LDL against further oxidative modification.

Adult↗
PubMed1995

Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage.

BACKGROUND: It has been hypothesized that the pathogenesis of diseases induced by cigarette smoking involves oxidative damage by free radicals. However, definitive evidence that smoking causes the oxidative modification of target molecules in vivo is lacking. We conducted a study to determine whether the production of F2-isoprostanes, which are novel products of lipid peroxidation, is enhanced in persons who smoke. METHODS: We measured the levels of free F2-isoprostanes in plasma, the levels of F2-isoprostanes esterified to plasma lipids, and the urinary excretion of metabolites of F2-isoprostanes in 10 smokers and 10 nonsmokers matched for age and sex. The short-term effects of smoking (three cigarettes smoked over 30 minutes) and the effects of two weeks of abstinence from smoking on levels of F2-isoprostanes in the circulation were also determined in the smokers. RESULTS: Plasma levels of free and esterified F2-isoprostanes were significantly higher in the smokers (242 +/- 147 and 574 +/- 217 pmol per liter, respectively) than in the nonsmokers (103 +/- 19 and 345 +/- 65 pmol per liter; P = 0.02 for free F2-isoprostanes and P = 0.03 for esterified F2-isoprostanes). Smoking had no short-term effects on the circulating levels of F2-isoprostanes. However, the levels of free and esterified F2-isoprostanes fell significantly after two weeks of abstinence from smoking (250 +/- 156 and 624 +/- 214 pmol per liter, respectively, before the cessation of smoking, as compared with 156 +/- 67 and 469 +/- 108 pmol per liter after two weeks' cessation; P = 0.03 for free F2-isoprostanes and P = 0.02 for esterified F2-isoprostanes). CONCLUSIONS: The increased levels of F2-isoprostanes in the circulation of persons who smoke support the hypothesis that smoking can cause the oxidative modification of important biologic molecules in vivo.

Adult↗
PubMed1995

Reduction of copper, but not iron, by human low density lipoprotein (LDL). Implications for metal ion-dependent oxidative modification of LDL.

Cell-mediated oxidative modification of human low density lipoprotein (LDL), most likely an important early step in atherosclerosis, requires redox active metal ions such as copper or iron. We have previously shown that iron-dependent, in contrast to copper-dependent, oxidative modification of LDL requires superoxide, a physiological reductant. In the present study, we sought to explain these discrepant results. LDL was incubated at 37 degrees C with Cu2+ (10 microM) and bathocuproine (BC, 360 microM), an indicator molecule which specifically complexes Cu+, but not Cu2+. In a time- and concentration-dependent manner, LDL reduced Cu2+ to Cu+. An LDL concentration as low as 10 micrograms of protein/ml (about 20 nM) reduced about 7 microM Cu2+ within 1 h of incubation. Complexation of the Cu+ formed under these conditions with BC significantly inhibited oxidative modification of LDL, as assessed by agarose gel electrophoresis. Preincubation of LDL with N-ethylmaleimide had no effect on the rate and extent of Cu2+ reduction nor LDL oxidation, indicating that free sulfhydryl groups associated with apolipoprotein B are not involved. Addition of either superoxide dismutase or catalase or increasing the alpha-tocopherol content of LDL from 11.8 +/- 3.0 to 24.4 +/- 2.8 nmol/mg of protein also had no significant effect on the kinetics of Cu2+ reduction by LDL. In contrast, incubation of LDL with Fe(3+)-citrate (10 microM) and the indicator bathophenanthroline (BP, 360 microM) resulted in no significant Fe2+ formation, even at LDL concentrations as high as 200 micrograms of protein/ml. However, incubation of LDL with Fe(3+)-citrate and an enzymatic source of superoxide led to rapid formation of Fe2+ and consequent oxidative modification of LDL. Addition of BP inhibited iron-mediated LDL oxidation under these conditions. Our results indicate that reduced metal ions are important mediators of LDL oxidation, and that LDL specifically reduces Cu2+, but not Fe3+. These data, therefore, help explain why copper, in addition to being chemically more reactive, is more potent than iron at mediating LDL oxidation.

Copper↗
PubMed1995

Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E.

BACKGROUND: The ability of oxidized LDL (oxLDL) to stimulate leukocyte-endothelium interaction is considered to be an important aspect of its proatherogenic action. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we have previously shown that systemic administration of oxLDL stimulates leukocyte adhesion to microvascular endothelium through a mechanism that involves the generation and action of reactive oxygen species (ROS). METHODS AND RESULTS: Through the combined use of scanning electron microscopy and intravital microscopy in the same animal model, we demonstrate that oxLDL-induced leukocyte adhesion is not confined to the microcirculation but can also be observed on aortic endothelium. OxLDL-induced leukocyte adhesion to both microvascular and macrovascular endothelium was almost entirely prevented by pretreatment of the hamsters with dietary or intravenous vitamin C, which has the capacity to scavenge and neutralize ROS (arterioles: 20.5 +/- 16.4 cells/mm2 [diet] and 16.3 +/- 23.8 cells/mm2 [IV] versus 74.2 +/- 47.5 cells/mm2 [control, P < .01]; aorta: 1.0 +/- 0.4 cells/mm2 [diet] and 1.1 +/- 0.5 cells/mm2 [IV] versus 14.7 +/- 6.0 cells/mm2 [control, P < .01], 15 minutes after oxLDL, n = 7 animals per group). Vitamin C pretreatment also completely prevented oxLDL-induced leukocyte-platelet aggregate formation in the blood-stream but did not affect leukocyte rolling along the microvascular endothelium. No inhibitory effect on any of the studied parameters was observed as a result of pretreatment of the animals with the lipid-soluble antioxidants vitamin E and probucol. CONCLUSIONS: The protective effects of vitamin C on oxLDL-induced leukocyte adhesion and aggregate formation were seen at vitamin C plasma levels that can easily be reached in humans by diet or supplementation, suggesting that this could be one of the mechanisms by which vitamin C contributes to the well-documented protraction of atherogenesis as observed in large epidemiological surveys.

Animals↗
PubMed1995

The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion.

BACKGROUND: Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction, which may contribute to ischemic cardiac events. Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown. METHODS: We randomly assigned 49 patients (mean serum cholesterol level, 209 +/- 33 mg per deciliter [5.40 +/- 0.85 mmol per liter]) to receive one of three treatments: an American Heart Association Step 1 diet (the diet group, 11 patients); lovastatin and cholestyramine (the low-density lipoprotein [LDL]-lowering group, 21 patients); or lovastatin and probucol (the LDL-lowering-antioxidant group, 17 patients). Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine (10(-8) to 10(-6) M) was assessed at base line and after one year of therapy. Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal. RESULTS: Treatment resulted in significant reductions in LDL cholesterol levels of 41 +/- 22 percent in the LDL-lowering-antioxidant group and 38 +/- 20 percent in the LDL-lowering group (P < 0.001 vs. the diet group). The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent, respectively, in the LDL-lowering-antioxidant group, -15 and -6 percent in the LDL-lowering group, and -14 and -19 percent in the diet group (P < 0.01 for the LDL-lowering-antioxidant group vs. the diet group; P = 0.08 for the LDL-lowering group vs. the diet group). (The negative numbers indicate vasoconstriction). Thus, the greatest improvement in the vasoconstrictor response was seen in the LDL-lowering-antioxidant group. CONCLUSIONS: The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implications for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy.

Acetylcholine↗
PubMed1995

Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation.

The inhibition of low density lipoprotein (LDL) oxidation has been postulated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Available data on the ability of beta-carotene to inhibit LDL oxidation are conflicting. We examined the role of in vivo and in vitro supplementation with beta-carotene on metal ion-dependent (cupric ions, Cu2+) and metal ion-independent (2,2'-azobis[2-amidinopropane]dihydrochloride, AAPH) oxidation of LDL as measured by the formation of conjugated dienes (absorbance at 234 nm). Sixteen subjects were supplemented with 50-100 mg of beta-carotene on alternate days for 3 weeks following a week-long loading dose of 100 mg/day. Plasma beta-carotene levels rose 5.5-fold, while LDL beta-carotene levels rose 8.5-fold. Oxidation of LDL by Cu2+ or AAPH was not significantly delayed after in vivo supplementation with beta-carotene compared with baseline. For AAPH, the lag phase (in minutes) was 75 +/- 8 at baseline and 83 +/- 14 after supplementation (P = 0.07). For Cu2+, the lag phase was 172 +/- 41 at baseline and decreased to 130 +/- 24 after supplementation (P < 0.01). Similarly, no protective effect against Cu(2+)-induced oxidation was observed when beta-carotene was added to LDL in vitro. Supplementation of plasma with beta-carotene in vitro prior to LDL isolation also did not enhance LDL's resistance to Cu(2+)- or AAPH-induced oxidation, despite a 5-fold increase in LDL beta-carotene levels over vehicle control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Dietary restriction delays cataract and reduces ascorbate levels in Emory mice.

Dietary restriction can effectively extend lifespan and retard many age-related debilities. One hypothesis to explain the beneficial effects of dietary restriction is that it prolongs maintenance of cellular homeostasis by limiting endogenous oxidative stress and preserves oxidative defense mechanisms during aging. Ascorbate, a primary antioxidant, may play a major role in preventing oxidative damage. Ascorbate levels were determined in dietary restricted (R) and control (C) Emory mice, a strain which develops age-related cataract due in part to oxidative damage to lens proteins. Mice which consumed a diet restricted by 40% in calories had lower ascorbate concentrations in plasma, liver and kidney. Nevertheless, R animals showed significantly delayed progression of cataract which extended over the entire second half of life. The R diet did not result in different ascorbate levels in this lens. Aging was associated with a decrease in ascorbate in all the examined tissues except lens of both the R and C groups. It is not clear from these data that ascorbate is a prominent factor in the delay of cataract formation or other debilities in R Emory mice. However, it also appears unlikely that lens ascorbate is cataractogenic.

Aging↗
PubMed1995

Cardiovascular disease and nutrient antioxidants: role of low-density lipoprotein oxidation.

Increasing evidence indicates that oxidative modification of low-density lipoprotein (LDL) is causally related to atherosclerosis. Oxidatively modified LDL (oxLDL), in contrast to native LDL, is taken up avidly by macrophages, leading to formation of lipid-laden foam cells. Foam cells are pathognomonic of the atherosclerotic fatty streak. Modified LDL may also promote atherosclerosis by many other mechanisms, such as recruitment and retention of monocyte-macrophages, T-lymphocytes, and smooth muscle cells in the arterial intima, and cytotoxicity toward endothelial cells and macrophage-derived foam cells. The "oxidation hypothesis of atherosclerosis" is supported by a number of in vivo findings, such as the presence of oxLDL in atherosclerotic lesions, and increased titers of autoantibodies against modified LDL in patients with atherosclerosis. As a corollary of the oxidation hypothesis of atherosclerosis, antioxidants that can inhibit LDL oxidation may act as antiatherogens. This conception is supported by animal studies showing that antioxidants such as probucol, butylated hydroxytoluene, and alpha-tocopherol can slow the progression of atherosclerosis. Epidemiological and clinical data indicate a protective role of dietary antioxidants against cardiovascular disease, including vitamin E, beta-carotene, and vitamin C. Likewise, basic research studies on LDL oxidation have demonstrated a protective role for antioxidants, present either in the aqueous environment of LDL or associated with the lipoprotein itself. More studies are needed to establish the effectiveness and determine the required doses of specific antioxidants to prevent and possibly treat cardiovascular disease.

Antioxidants↗
PubMed1995

Discrimination in absorption or transport of beta-carotene isomers after oral supplementation with either all-trans- or 9-cis-beta-carotene.

Human subjects (n = 24) were supplemented with 100 mg beta-carotene/d for 6 d, either as synthetic all-trans-beta-carotene or a natural beta-carotene preparation derived from the alga Dunaliella salina, which consists of a 50:50 mixture of all-trans- and 6-cis-beta-carotene. This loading dose was followed by a 23-d maintenance dose consisting of alternate-day supplementation with 50 mg all-trans-beta-carotene or either 66 or 100 mg of the natural 50:50 isomeric mixture. The loading dose resulted in significant increases in plasma concentrations of both isomers, with the all-trans-beta-carotene-supplemented group showing a 7.2- and 5.0-fold increase in the all-trans and 9-cis concentrations in plasma, respectively. The group receiving the 50:50 mixture showed a 4.0- and 3.7-fold increase in the all-trans and 9-cis concentrations in plasma, respectively, without any apparent dose-dependency. However, even with the 50:50 mixture, the 9-cis concentrations were only a small fraction of the total plasma beta-carotene. Results after an additional 23-d period of alternate-day supplementation were not significantly different from those described above for the 6-d supplementation. Increases in low-density-lipoprotein concentrations of total beta-carotene correlated strongly with the increases seen in plasma concentrations. Lipid-soluble antioxidants vitamin E and ubiquinol were unaffected by beta-carotene supplementation. However, the amount of lycopene in the low-density lipoprotein decreased during this supplementation period. A strong discrimination between these two geometric isomers of beta-carotene was demonstrated, although the tissue site of discrimination was not determined.

Administration, Oral↗
PubMed1995

Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation.

Excess vascular oxidative stress and the local formation of oxidized LDL (ox-LDL) have been implicated in the development of impaired endothelium-dependent arterial relaxation in hypercholesterolemia and atherosclerosis. Dietary antioxidants limit LDL oxidation in vitro and treatment of cholesterol-fed rabbits with dietary antioxidants preserves endothelium-derived relaxing factor (EDRF) action. To investigate the mechanism(s) responsible for these observations, we examined EDRF action, vascular oxidative stress, and antioxidant protection in male New Zealand White rabbits using four dietary treatments. Animals consumed standard chow (chow group) or chow supplemented with: (a) 0.5% cholesterol (0.5% cholesterol group); (b) 1% cholesterol (1% cholesterol group); or (c) 1% cholesterol and 1% probucol (probucol group). After 28 d of dietary treatment, segments of thoracic aorta from the 0.5 and 1% cholesterol groups demonstrated impairment of acetylcholine-mediated endothelium-dependent arterial relaxation compared to chow-fed animals (57 +/- 11% and 45 +/- 9% vs 78 +/- 3%, respectively; P < 0.05). In contrast, vessels from the probucol group demonstrated normal relaxation to acetylcholine (83 +/- 5%). Plasma cholesterol levels and the extent of atherosclerosis were similar among all cholesterol-fed groups. Probucol treatment was associated a threefold increase in LDL resistance to copper-induced oxidative modification (P < 0.05) and a reduction in tissue lipid peroxidation (as assessed by thiobarbituric acid-reactive substances; P < 0.05) compared to animals fed cholesterol alone. Most importantly, both of these changes were strongly correlated with preserved EDRF action. Moreover, cholesterol feeding was associated with a dose-dependent increase in vascular superoxide generation and lysophosphatidylcholine content, both of which were prevented by probucol treatment. From these findings, we conclude that probucol, a lipid-soluble antioxidant, preserves EDRF action in cholesterol-fed rabbits in association with limiting vascular oxidative stress and superoxide generation.

Animals↗
PubMed1995

Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.

GSH peroxidase (Px) catalyzes the reduction of lipid hydroperoxides (LOOH), known metabolic products of platelets and vascular cells. Because interactions between these cells are modulated by nitric oxide (NO) and LOOH inactivate NO, we investigated the effect of GSH-Px on the inhibition of platelet function by the naturally occurring S-nitrosothiol, S-nitroso-glutathione (SNO-Glu). Concentrations of SNO-Glu that alone did not inhibit platelet function (subthreshold inhibitory concentrations) were added to platelet-rich plasma together with GSH-Px (0.2-20 U/ml); this led to a dose-dependent inhibition of platelet aggregation with an IC50 of 0.6 U/ml GSH-Px. In the presence of subthreshold inhibitory concentrations of SNO-Glu, the LOOH, 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid, increased platelet aggregation, an effect reversed by GSH-Px. Glutathione and SNO-Glu were equally effective as cosubstrates for GSH-Px. Incubation of SNO-Glu with GSH-Px for 1 min led to a 48.5% decrease in the concentration of SNO-Glu. Incubation of SNO-Glu with serum albumin led to the formation of S-nitroso-albumin, an effect enhanced by GSH-Px. These observations suggest that GSH-Px has two functions: reduction of LOOH, thereby preventing inactivation of NO, and metabolism of SNO-Glu, thereby liberating NO and/or supporting further transnitrosation reactions.

Blood Platelets↗