Vitamin E, Selenium, Trolox C, Ascorbic Acid Palmitate, Acetylcysteine, Coenzyme Q, β-Carotene, Canthaxanthin, and (+)-Catechin Protect Against Oxidative Damage to Kidney, Heart, Lung and Spleen

Male Sprague-Dawley rats were fed diets that varied qualitatively and quantitatively in antioxidants. Kidney, heart, lung, and spleen homogenates were incubated at 37°C with and without hydroperoxide or Fe⁺². Protection of antioxidants against oxidative damage to tissue was determined by measurement of oxidized heme proteins. Tissues from rats supplemented with dietary vitamin E and selenium showed protection compared to tissues from rats on the basal diet. Tissues from rats with diets containing larger quantities of antioxidants and both fat soluble antioxidants: vitamin E, β-carotene, coenzyme Q₁₀, ascorbic acid 6-palmitate and water soluble antioxidants: selenium, trolox C, acetylcysteine, coenzyme Q₀, (+)-catechin, showed the highest protection.     

Effects of a carotene-deficient diet on measures of oxidative susceptibility and superoxide dismutase activity in adult women

The effect of consuming a low carotene diet (≈60 μg carotene/day) on oxidative susceptibility and superoxide dismutase (SOD) activity in women living in a metabolic research unit was evaluated. The diet had sufficient vitamins A, E, and C. The women ate the diet supplemented with 1500 μg/day β-carotene for 4 days (baseline), then the unsupplemented diet for 68 days (depletion), followed by the diet supplemented with > 15,000 μg/day carotene for 28 days (repletion). Production of hexanal, pentanal, and pentane by copper-oxidased plasma low density lipoproteins from carotene-depleted women was greater than their production of these compounds when repleted with carotene. Erythrocyte SOD activity was depressed in carotene-depleted women; it recovered with repletion. Thiobarbituric acid reactive substances in plasma of carotene-depleted women were elevated and diminished with repletion. Dietary carotene seems to be needed, not only as a precursor of vitamin A, but also to inhibit oxidative damage and decrease oxidation susceptibility.     

Induction of 1,N(2)-etheno-2'-deoxyguanosine in DNA exposed to beta-carotene oxidation products

Epidemiological studies testing the effect of β-carotene in humans have found a relative risk for lung cancer in smokers supplemented with β-carotene. We investigated the reactions of retinal and β-apo-8′-carotenal, two β-carotene oxidation products, with 2′-deoxyguanosine to evaluate their DNA damaging potential. A known mutagenic adduct, 1,N²-etheno-2′-deoxyguanosine, was isolated and characterized on the basis of its spectroscopic features. After treatment of calf thymus DNA with β-carotene or β-carotene oxidation products, significantly increased levels of 1,N²-etheno-2′-deoxyguanosine and 8-oxo-7,8-dihydro-2′-deoxyguanosine were quantified in DNA. These lesions are believed to be important in the development of human cancers. The results reported here may contribute toward an understanding of the biological effects of β-carotene oxidation products.     

Benign coxsackievirus damages heart muscle in iron-loaded vitamin E-deficient mice

Several oxidative stressors (dietary selenium deficiency, dietary vitamin E deficiency coupled with fish oil feeding, genetic reduction of glutathione peroxidase activity) allow a normally benign coxsackievirus B3 (CVB3/0) to damage heart muscle in host mice. This study investigated whether dietary iron overload, another oxidant stress, would also permit CVB3/0 to exert a cardiopathologic effect in vitamin E-deficient (-VE) mice. Four groups of mice were fed either a -VE or a +VE diet containing either an adequate or an excessive (30x) amount of iron. After 4 weeks of feeding, the mice were inoculated with CVB3/0 and heart damage was assessed at various times postinfection. Mice fed a diet sufficient in VE with excess iron developed heart damage equivalent to mice fed a diet deficient in vitamin E without excess iron. However, severe heart damage occurred in the group fed a diet deficient in VE with excess iron, which was the most pro-oxidative diet. The highest heart viral titers were found in mice fed the -VE/excessive iron diet. However, the extent of heart damage did not always correlate with the formation of TBARS in liver homogenates. Further research is needed to clarify the role of oxidative stress and iron overload in determining the course of viral infection.     

Dietary vitamin E reduces labile iron in rat tissues

Previous studies have shown that dietary vitamin E reduced generation and/or levels of superoxide. As superoxide has potential to release iron from its transport and storage proteins, and labile or available form of iron is capable of catalyzing the formation of reactive hydroxyl radicals, the effect of dietary vitamin E on labile iron pool was studied in rats. One-month-old Sprague-Dawley male and female rats were fed a basal vitamin E-deficient diet supplemented with 0, 20, 200, or 2,000 IU vitamin E/kg diet for 90 days. The levels of labile iron were measured in the liver, kidney, spleen, heart and skeletal muscle. Additionally, the levels of lipid peroxidation products were measured. The results showed that, except for labile iron in the heart of male rats, dietary vitamin E dose dependently reduced the levels of labile iron and lipid peroxidation products in all tissues of male and female rats. The findings suggest that dietary vitamin E may protect against oxidative tissue damage by reducing the generation and/or level of superoxide, which in turn attenuates the release of iron from its protein complexes.     

Photoprotective potential of lycopene, β-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts

The photoprotective potential of the dietary antioxidants vitamin C, vitamin E, lycopene, β-carotene, and the rosemary polyphenol, carnosic acid, was tested in human dermal fibroblasts exposed to ultraviolet-A (UVA) light. The carotenoids were prepared in special nanoparticle formulations together with vitamin C and/or vitamin E. Nanoparticle formulations, in contrast to dimethylsulphoxide, stablized lycopene in the cell culture medium and allowed efficient cellular uptake. The presence of vitamin E in the formulation further increased the stability and cellular uptake of lycopene. UVA irradiation of the human skin fibroblasts led to a 10–15-fold rise in metalloproteinase 1 (MMP-1) mRNA. This rise was suppressed in the presence of low μM concentrations of vitamin E, vitamin C, or carnosic acid but not with β-carotene or lycopene. Indeed, in the presence of 0.5–1.0 μM β-carotene or lycopene, the UVA-induced MMP-1 mRNA was further increased by 1.5–2-fold. This increase was totally suppressed when vitamin E was included in the nanoparticle formulation. Heme-oxygenase 1 (HO-1) mRNA expression was strongly induced by UVA irradiation but none of the antioxidants inhibited this effect at the concentrations used in this study. Indeed, β-carotene or lycopene (0.5–1.0 μM) led to a further 1.5-fold rise in the UVA-induced HO-1 mRNA levels. In conclusion, vitamin C, vitamin E, and carnosic acid showed photoprotective potential. Lycopene and β-carotene did not protect on their own but in the presence of vitamin E, their stability in culture was improved and the rise in MMP-1 mRNA expression was suppressed, suggesting a requirement for antioxidant protection of the carotenoids against formation of oxidative derivatives that can influence the cellular and molecular responses.     

Pro-oxidative effect of beta-carotene and the interaction with flavonoids on UVA-induced DNA strand breaks in mouse fibroblast C3H10T1/2 cells

It has been suggested that β-carotene itself is unstable under certain conditions and that a combination of antioxidants may prevent the pro-oxidative effects of β-carotene. Thus, the present study aimed to investigate the interaction of β-carotene with three flavonoids—naringin, rutin and quercetin—on DNA damage induced by ultraviolet A (UVA) in C3H10T1/2 cells, a mouse embryo fibroblast. The cells were preincubated with β-carotene and/or flavonoid for 1 h followed by UVA irradiation, and DNA damage was measured using comet assay. We showed that β-carotene at 20 μM enhanced DNA damage (by 35%; P<.05) induced by UVA (7.6 kJ/m²), whereas naringin, rutin and quercetin significantly decreased UVA-induced DNA damage. When each flavonoid was combined with β-carotene during preincubation, UVA-induced cellular DNA damage was significantly suppressed and the effects were in the order of naringin≥rutin>quercetin. The flavonoids decreased UVA-induced oxidation of preincorporated β-carotene in the same order. Using electron spin resonance spectroscopy, we showed that the ability of these flavonoids to quench singlet oxygen was consistent with protection against DNA damage and β-carotene oxidation. All three flavonoids had some absorption at the UVA range (320–380 nm), but the effects were opposite to those on DNA damage and β-carotene oxidation. Taken together, this cell culture study demonstrates an interaction between flavonoids and β-carotene in UVA-induced DNA damage, and the results suggest that a combination of β-carotene with naringin, rutin or quercetin may increase the safety of β-carotene.     

Ex vivo Assessment of Lymphocyte Antioxidant Status Using the Comet Assay

Lymphocytes were isolated from volunteers before and after receiving a single supplement of vitamin C, vitamin E or β-carotene. The lymphocytes were treated with H₂O₂, and DNA strand breaks were measured by single cell gel electrophoresis (the comet assay). Significant protection against oxidative DNA damage was evident 2-4 h after vitamin C intake, and 18-24 h after consumption of the other antioxidants. Lymphocytes from smokers were more sensitive to DNA damage than those from non-smokers, and they showed at least as great a protective effect with antioxidants.     

The role of antioxidant nutrients in preventing hyperbaric oxygen damage to the retina

Vitamin E and selenium play essential roles in preventing in vivo lipid peroxidation and free radical damage. Hyperbaric oxygen (HBO) treatment adversely affected the electroretinograms (ERGs) of rats fed a diet deficient in both vitamin E and selenium (the basal or B diet) or a diet deficient in vitamin E alone (B + Se diet). After 4 weeks of HBO treatment (3.0 ATA or 100% oxygen, 1.5 hours per day, 5 day/week) rats fed the B diet deficient in vitamin E and selenium for 6 weeks showed decreased (p less than 0.05) a-wave amplitudes, 85 +/- 9 microvolts (microV), n = 11, compared with a-waves recorded (150 +/- 10 microV, n = 21) for age matched rats fed an identical diet for 6 weeks but not treated with HBO. After 15 weeks of HBO treatment, rats fed the B + Se diet deficient in vitamin E alone showed decreased (p less than 0.01) a-wave (61 +/- 9 microV, n = 4) and b-wave (253 +/- 23 microV, n = 4) amplitudes compared with a-wave (115 +/- 7 microV, n = 4) and b-wave amplitudes (450 +/- 35 microV, n = 4) for age matched rats fed the same diet but not treated with HBO. Decreased a- or b-wave amplitudes provide evidence of retinal damage. Rats fed a diet supplemented with vitamin E and selenium or vitamin E alone showed no decreases in either a- or b-wave amplitudes after 15 weeks of HBO treatment.     

饲料硒和维生素E对大鼠机体抗氧化能力的影响

 用克山病病区粮配成基础低硒饲料,补充硒和/或维生素E组成四种不同水平的饲料,饲喂雄性断乳大鼠,观察其对机体抗氧化能力的影响。评价指标是用抗坏血酸诱发的红细胞溶血率、被O~-_2(超氧阴离子)氧化的血红蛋白量和组织中的TBA值。动物饲养13周后,自尾静脉取血,测定溶血率和血红蛋白被氧化的百分率,和全血SeGSHPx(含硒谷胱甘肽过氧化物酶)活力。15周后将动物断头杀死,立即取出心脏和肝脏测定SeGSHPx活力和TBA值。结果表明在克山病病区粮的饲料中补充硒或维生素E,或者二者同时补充均明显提高组织中的SeGSHPx活力和降低组织中的TBA值。不论在硒缺乏时或硒充足时,饲料中补充维生素E显著降低抗坏血酸诱发的红细胞溶血率,对O~-_2氧化血红蛋白无保护作用。在维生素E缺乏时,仅补充硒对溶血无作用。不论饲料中维生素E缺乏或者充足,补充硒对O~-_1氧化血红蛋白均有显著保护作用。     

Parameters of dietary selenium and vitamin E deficiency in growing rabbits.

4 x 5 growing female rabbits (New Zealand White) with an initial live weight of 610 +/- 62 g were fed a torula yeast based semisynthetic diet low in selenium (<0.03 mg/kg diet) and containing <2 mg alpha-tocopherol per kg (group I). Group II received a vitamin E supplementation of 150 mg alpha-tocopherylacetate per kg diet, whereas for group III 0.40 mg Se as Na-selenite and for group IV both supplements were added. Selenium status and parameters of tissue damage were analyzed after 10 weeks on experiment (live weight 2,355 +/- 145 g). Selenium depletion of the Se deficient rabbits (groups I and II) was indicated by a significantly lower plasma Se content (group I: 38.3 +/- 6.23 microg Se/mL plasma, group II: 42.6 +/- 9.77, group III: 149 +/- 33.4, group IV: 126 +/- 6.45) and a significantly lower liver Se content (group I: 89.4 +/- 18.2 microg/kg fresh matter, group II: 111 +/- 26.2) as compared to the Se supplemented groups III (983 +/- 204) and IV (926 +/- 73.9). After 5 weeks on the experimental diets differences in the development of plasma glutathione peroxidase were observed. As compared to the initial status group (45.2 +/- 4.50) pGPx activity in mU/mg protein was decreased in group I (19.1 +/- 7.08), remained almost stable in the vitamin E supplemented group II (46.3 +/- 11.2) whereas an elevated enzyme activity was measured in the Se supplemented groups III (62.4 +/- 23.9) and IV (106 +/- 19.9). In the rabbit organs investigated 10 weeks of Se deficiency caused a significant loss of Se dependent cellular glutathione peroxidase activity (GPx1) of 94% (liver), 80% (kidney), 50% (heart muscle) and 60% (musculus longissimus dorsi) in comparison to Se supplemented control animals. Damage of cellular lipids and proteins in the liver was due to either Se or vitamin E deficiency. However damage was most severe under conditions of a combined Se and vitamin E deficiency. It can be concluded that the activity of plasma glutathione peroxidase is a sensitive indicator of Se deficiency in rabbits. The loss of GPx1 activity indicates the selenium depletion in various rabbit organs. Both selenium and vitamin E are essential and highly efficient antioxidants which protect rabbits against lipid and protein oxidation.     

Coxsackievirus B3-resistant mice become susceptible in Se/vitamin E deficiency

The severity of the heart damage caused by a coxsackievirus infection in mice is determined by several factors, including the genotype of the infecting virus as well as the genetic background of the infected host. Earlier work by us showed that the cardiovirulence of a given coxsackievirus genotype could be increased substantially by feeding the host a diet nutritionally deficient in either selenium or vitamin E. Here we report that host genetic background as a determinant of viral infection outcome is superseded by feeding the host a diet nutritionally deficient in both selenium and vitamin E. Mice of the C57Bl/6 strain, normally resistant to coxsackievirus B3-induced myocarditis, become susceptible when fed such a doubly deficient diet. Our results demonstrate the powerful influence of host nutritional status on the course of viral infection compared to other variables traditionally considered to play major roles in determining the extent of virally induced inflammatory heart disease.     

Purification, composition, and some properties of rat liver carbamyl phosphate synthetase (ammonia).

Hepatic microsomes prepared from vitamin E deficient and supplemented rats were analyzed for cytochrome P-450 content and drug metabolizing activity. Reduced levels of benzo[α]pyrene hydroxylase and ethylmorphine N-demethylase activities were observed in microsomes derived from rats fed a diet deficient in vitamin E compared to those of control rats. NADPH-mediated destruction of P-450, and pentobarbital and zoxazolamine sleeping times were similar in the two groups. Induction with 3-methylcholanthrene raised the levels of benzo[α]pyrene hydroxylase activity of both supplemented and deficient rats to the same absolute levels. No differences were noted in cytochrome P-450 or P-448 content between control and tocopherol deficient rats, nor did the activity of liver catalase differ between the two dietary groups. Thus, these studies did not demonstrate any impairment of heme protein synthesis in vitamin E deficient rats.     

Carotenoid oxidative degradation products inhibit Na+-K+-ATPase

This study investigates the biological significance of carotenoid oxidation products using inhibition of Na⁺-K⁺-ATPase activity as an index. β-Carotene was completely oxidized by hypochlorous acid and the oxidation products were analyzed by capillary gasliquid chromatography and high performance liquid chromatography. The Na⁺-K⁺-ATPase activity was assayed in the presence of these oxidized carotenoids and was rapidly and potently inhibited. This was demonstrated for a mixture of β-carotene oxidative breakdown products, β-Apo-10'-carotenal and retinal. Most of the β-carotene oxidation products were identified as aldehydic. The concentration of the oxidized carotenoid mixture that inhibited Na⁺-K⁺-ATPase activity by 50% (IC₅₀) was equivalent to 10μM non-degraded β-carotene, whereas the IC₅₀ for 4-hydroxy-2-nonenal, a major lipid peroxidation product, was 120 μM. Carotenoid oxidation products are more potent inhibitors of Na⁺-K⁺-ATPase than 4-hydroxy-2-nonenal. Enzyme activity was only partially restored with hydroxylamine and/or β-mercaptoethanol. Thus, in vitro binding of carotenoid oxidation products results in strong enzyme inhibition. These data indicate the potential toxicity of oxidative carotenoid metabolites and their activity on key enzyme regulators and signal modulators.     

Dietary selenium status and plasma thyroid hormones in chicks

Experiments were conducted to study the effect of marginal levels of selenium and vitamin E on plasma thyroid hormones of meattype chicks. Plasma thyroxine (T₄) was significantly increased when a semipurified diet was supplemented with either selenium or vitamin E. Triiodothyronine (T₃) was also significantly increased by vitamin E and in one experiment with selenium supplementation. No significant increase in these hormones was observed in birds fed a corn-soybean-meal diet supplemented with these nutrients. Plasma corticosterone level was reduced and weight of the bursa of Fabricius increased by selenium or vitamin E supplementation. These nutrients may be necessary for providing the optimum thyroid conditions for activity of thyroid peroxidase.     

Effect of a Single Bout of Exercise and β-Carotene Supplementation on the Urinary Excretion of 8-Hydroxy-deoxyguanosine in Humans

We investigated the effects of acute exhaustive exercise and β-carotene supplementation on urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion in healthy nonsmoking men. Fourteen untrained male (19-22 years old) volunteers participated in a double blind design. The subjects were randomly assigned to either the β-carotene or placebo supplement group. Eight subjects were given 30 mg of β-carotene per day for 1 month, while six subjects were given a placebo for the same period. All subjects performed incremental exercise to exhaustion on a bicycle ergometer both before and after the 1-month β-carotene supplementation period. The blood lactate and pyruvate concentrations significantly increased immediately after exercise in both groups. The baseline plasma p-carotene concentration was significantly 17-fold higher after β-carotene supplementation. The plasma β-carotene decreased immediately after both trials of exercise, suggesting that β-carotene may contribute to the protection of the increasing oxidative stress during exercise. Both plasma hypoxanthine and xanthine increased immediately after exercise before and after supplementation. This thus suggests that both trials of exercise might enhance the oxidative stress. The 24-h urinary excretion of 8-OHdG was unchanged for 3 days after exercise before and after supplementation in both groups. However, the baseline urinary excretion of 8-OHdG before exercise tended to be lower after β-carotene supplementation. These results thus suggest that a single bout of incremental exercise does not induce the oxidative DNA damage, while β-carotene supplementation may attenuate it.     

Comparison of selenium level and glutathione peroxidase activity in tissues of vitamin B6-deficient rats fed sodium selenite or DL-selenomethionine

The effect of vitamin B₆ on the levels of tissue selenium (Se) and glutathione peroxidase (GSH-Px) was studied. Male Wistar 4-week-old rats were fed a vitamin B₆-Se-deficient basal diet for 2 weeks, then divided into 10 groups of five or six rats and fed their respective diets for 4 weeks. The experimental design was a 2×2×2 factorial with two levels of vitamin B₆, two forms of Se, and two levels of Se, plus two extra groups (vitamin B₆-supplemented and deficient without Se). Vitamin B₆ was 0 and 250 μg pyridoxine-HCl/100 g of diet; Se forms were Na₂SeO₃ and DL-selenomethionine; Se levels were 0.5 and 5.0 mg Se/kg of diet. Regardless of form or level of Se, vitamin B₆-deficient rats had lower body weights and organ weights than vitamin B₆-supplemented rats. At 5.0 mg Se/kg of diet, Na₂SeO₃ caused a further depression. Vitamin B₆ deficiency resulted in a higher Se level and GSH-Px activity in plasma of rats fed selenomethionine. However, Se content an GSH-Px activity in erythrocytes were significantly elevated in vitamin B₆-supplemented rats compared with vitamin B₆-deficient rats. Se levels in muscle and heart were significantly lower in vitamin B₆-deficient groups fed Na₂SeO₃ than in vitamin B₆-supplemented groups. Vitamin B₆-deficient rats fed selenomethionine had higher Se levels in muscle, heart, spleen, liver, and kidneys than vitamin B₆-supplemented rats. Activity of GSH-Px in muscle, heart, and spleen was significantly lower in vitamin B₆-deficient groups than in vitamin B₆-supplemented groups, regardless of form of Se. A significant decrease of GSH-Px in liver was observed in vitamin B₆-deficient rats fed selenomethionine compared with vitamin B₆-supplemented rats, whereas no significant decrease was observed in those fed Na₂SeO₃. These results suggest that vitamin B₆ is involved in the distribution and transportation of Se in body and the metabolism of selenomethionine in liver.     

Vitamin K dependent carboxylation of glutamate residues to gamma-carboxyglutamate in microsomes from spleen and testes: comparison with liver, lung, and kidney

Vitamin K dependent carboxylation of glutamate residues to gamma-carboxyglutamate was demonstrated in proteins of spleen and testes microsomes. The rate of carboxylation in spleen microsomes was 0.9% and testes 3% of that in liver microsomes per milligram of microsomal protein. For comparison the rates of carboxylation in lung and kidney microsomes were 17 and 8%, respectively, of the rate in liver microsomes. The high rate in liver microsomes may be due to a high carboxylase level as indicated by the high rate of peptide carboxylation in liver microsomes. Protein carboxylation in liver microsomes was linear for only 15 min while carboxylation in microsomes from extrahepatic tissue persisted much longer so that the total protein carboxylation in lung microsomes was 60%, kidney 18%, testes 12%, and spleen 9% of that occurring in liver microsomes. Protein carboxylation was higher in microsomes from extrahepatic tissues of rats fed a vitamin K deficient diet as compared to animals fed a vitamin K sufficient diet. Protein carboxylation in microsomes from extrahepatic tissues was greatly stimulated by manganese ions and was dependent upon the addition of dithioerythritol. NADH could partially replace the dithiol in spleen, testes, and lung, but NADH-dependent carboxylation was relatively low in kidney and liver microsomes. Dithiol-dependent carboxylation was completely blocked by 10 microM warfarin, but NADH-dependent carboxylation was only slightly inhibited by 100 microM warfarin. Menaquinone-3 was much more active than vitamin K1 in driving carboxylation. Solubilized microsomes catalyzed the carboxylation of glutamate residues to gamma-carboxyglutamate in a pentapeptide Phe-Leu-Glu-Glu-Leu. The rate of carboxylation in lung microsomes was 22%, testes 3.3%, kidney 1.9%, and spleen 1.6% of the rate in liver microsomes.     

The effect of selenium and vitamin E on microvascular permeability of rat organs

The effects of dietary sodium selenite and vitamin E on the microvascular permeability of rat organs such as heart, brain, kidney, liver and eye were investigated by using the Evans blue leakage method. Combined deficiency of selenium and vitamin E caused an increase in the permeability of the heart and eye with respect to their controls while it had no considerable effect on the permeability of other organs. On the other hand, toxic levels of selenium (4.2 mg/kg) in diet decreased the permeabilities in kidney, liver, and eye whereas this parameter of brain increased in the same animal group. These results suggested that low or high sodium selenite and vitamin E contents in diet could alter the microvascular permeability of different organs in different manners. It might be important to give reasonable explanations for the pathophysiology of some diseases that are characterized with organ damage and /or disfunction originated from selenium deficiency or toxicity.     

Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies

Vitamin E and carotenoids are known to act as antioxidants both in vitro and in vivo. In this review we present a series of studies in healthy subjects and in patients who exhibit either acute or chronic oxidative stress. In the EU-Commission funded VITAGE project we investigated the status and effects of vitamin E and carotenoids on oxidative stress in 300 healthy volunteers. Depletion studies limiting dietary vitamin E or carotenoid intake to 25% of the dietary reference intakes and subsequent repletion by supplementation with either large doses of vitamin E or intermediate doses of carotenoids showed significant changes in ex vivo LDL oxidizability, total plasma peroxide concentrations and urinary 8-oxo-7,8-dihydro-2^′-deoxyguanosine excretion. Patients on chronic hemodialysis present with oxidative stress in the presence of normal vitamin E but impaired vitamin C status and, due to anemia, need to be treated with parenteral iron. We studied the effects of a single oral dose of vitamin E taken 6 h prior to intravenous infusion of 100 mg iron, which exceeded the iron-binding capacity of transferrin. Vitamin E significantly reduced and in combination with a single dose of vitamin C completely abrogated acute oxidative stress induced by the iron load. Patients with cystic fibrosis are exposed to chronic oxidative stress due to an overproduction of reactive oxygen species as a result of neutrophil-dominated lung inflammation and impaired antioxidant status. Biochemical vitamin E and carotenoid deficiencies could be fully corrected even in the presence of fat malabsorption using intermediate doses of either RRR -tocopherol or all-rac -tocopheryl acetate and water-miscible all-trans β-carotene. Long-term supplementation reduced ex vivo LDL oxidizability, in vivo lipid peroxidation and lung inflammation.