Inhibition of oxidation of methyl linoleate in solution by vitamin E and vitamin C

The oxidation of methyl linoleate in solution initiated with azo compounds has been studied in the absence and presence of vitamin E and vitamin C. Both vitamin E and vitamin C acted as a chain-breaking antioxidant and they suppressed the oxidation and produced an induction period. The inhibition rate constant for the scavenging of peroxy radical was calculated at 37 degrees C as kinh = 5.1 X 10(5) M-1 s-1 and 7.5 X 10(4) M-1 s-1 for vitamin E and vitamin C, respectively. It was suggested that each vitamin E could trap two peroxy radicals, whereas vitamin C could trap only one peroxy radical under the reaction conditions employed in this study. When both vitamin E and vitamin C were present, the oxidation was suppressed quite efficiently and the apparent inhibition rate constant was obtained as kinh = 4.0 X 10(5) M-1 s-1. Furthermore, vitamin E remained almost unchanged and only vitamin C was consumed at the initial stage and vitamin E was consumed after vitamin C was exhausted. It was concluded that vitamin E trapped the peroxy radical and the resulting alpha-chromanoxy radical reacted with vitamin C to regenerate vitamin E.     

The effect of maternal and cord-blood vitamin C, vitamin E and lipid peroxide levels on newborn birth weight

Background Newborn birth weight has been shown to significantly correlate with the blood levels of vitamin C. Objective This study was planned to answer the question of why vitamin C levels correlate with birth weight; does such correlation reflect a protective effect of vitamin C on fetal growth, by its antioxidant characteristics or does it correspond to the nutritional status of both the mother and the fetus. We examined the hypothesis that maternal blood levels of vitamin C, but not vitamin E influence newborn birth weight. We determined maternal and newborn blood levels of vitamin C, vitamin E, and lipid peroxides (an index of oxidative insult) and the birth weights of full-term newborns delivered at our hospital. Results Compared with maternal blood levels, newborns have higher levels of vitamin C and lipid peroxides, but lower levels of vitamin E. There was a significant correlation in levels between mothers and their newborns for blood levels of vitamin C (r = 0.82, P < 0.01) and vitamin E (r = 0.61, P < 0.02) but not for lipid peroxides (r = 0.001). This suggests that maternal vitamin C and vitamin E intake can influence fetal vitamin C and vitamin E levels. Linear regression analysis shows a significant positive relationship between newborn birth weight and maternal plasma vitamin C (r = 0.51, P < 0.02). Similarly, there was a modest but significant positive relationship between newborn birth weights and newborn vitamin C levels (r = 0.61, P < 0.05). However, there was no relationship between maternal or fetal vitamin E or lipid peroxides levels and the newborn birth weight. Conclusions This study with a small number of subjects suggests a significant association between newborn birth weight and maternal and newborn plasma vitamin C levels. Lack of relationship between birth weight and vitamin E and lipid peroxides suggest that antioxidant function of vitamin C does not appear to have a major role in the effect of vitamin C on birth weight.     

Free radical-mediated chain oxidation of low density lipoprotein and its synergistic inhibition by vitamin E and vitamin C

The oxidation of human low density lipoprotein (LDL) initiated by free radical initiator and its inhibition by vitamin E and water-soluble antioxidants have been studied. It was found that the kinetic chain length was considerably larger than 1, suggesting that LDL was oxidized by a free radical chain mechanism. Vitamin E acted as a lipophilic chain-breaking antioxidant. Water-soluble chain-breaking antioxidants such as ascorbic acid and uric acid suppressed the oxidation of LDL initiated by aqueous radicals but they could not scavenge lipophilic radicals within LDL to break the chain propagation. Ascorbic acid acted as a synergistic antioxidant in conjunction with vitamin E.     

Modulation of the platelet thromboxane A2 and aortic prostacyclin synthesis by dietary selenium and vitamin E

Vitamin E and selenium (Se) interact synergistically as an important antioxidant defense mechanism. Se, an essential component of glutathione peroxidase (GSH-Px) and vitamin E decompose fatty acid hydroperoxides and hydrogen peroxides generated by free radical reactions. Vitamin E and GSH-Px may modulate arachidonic acid metabolism and the activity of cyclooxygenase enzymes by affecting peroxide concentration. The balance between arterial wall prostacyclin (PGI₂) production and platelet thromboxane (TX)A₂ directly influences platelet activity. In order to elucidate the differential role of dietary vitamin E and Se in aortic PGI₂ and platelet TXA₂ synthesis, 1-mo-old F344 rats were fed semipurified diets containing different levels of vitamin E (0, 30, 200 ppm) and Se (0, 0.1, 0.2 ppm) for 2 mo. Thromboxane B₂ (TXB₂) and 6-keto-PGF₁α, were measured by radioimmunoassay (RIA) after incubation of whole blood and aortic rings at 37°C for 10 and 30 min, respectively. Vitamin E deficiency reduced plasma vitamin E to 5–17% of control-fed rats, and supplementation increased it to 53% of the control-fed rats. Se supplementation in vitamin E-supplemented animals increased plasma GSH-Px by 17%, compared to vitamin E-deficient rats. Se and vitamin E supplementation did not have a similar effect on TXB₂ and PGI₂ synthesis. Se deficiency did not alter platelet TXB₂ synthesis, but significantly decreased aortic PGI₂ synthesis. It was necessary to supplement with both antioxidants in order to increase, PGI₂ synthesis. Se and vitamin E deficient groups had a higher TXB₂/PGI₂ ratio (0.17±0.08) compared to Se- and vitamin E-supplemented groups (0.03±0.01). These results confirm previous reports in humans and animals and are in accordance with epidemiological data indicating an inverse relationship between plasma Se and platelet aggregation. Thus, further suggesting that vitamin E and Se may have a specific role in controlling TXA₂ and PGI₂ synthesis.     

One-electron oxidation of Trolox C and vitamin E by peroxidases.

Direct reactions of peroxidases with Trolox C (a vitamin E analogue) and vitamin E were observed in 50% (v/v) methanol. The kinetic results revealed that the reaction of horseradish peroxidase intermediate Compound II with Trolox C and vitamin E was the rate-determining step, and the rate constants were estimated to be 1.7 x 10(3) and 5.1 x 10(2) M-1.s-1, respectively. Peroxidases catalyzed the one-electron oxidation of Trolox C and vitamin E, and the vitamin E phenoxyl radicals resulting from the peroxidase reactions were detected by continuous-flow ESR spectroscopy.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F₂-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the “Antioxidant Supplementation in Atherosclerosis Prevention” (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of d-α-tocopheryl acetate daily), both vitamins (CellaVie^®), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F₂-isoprostane concentration was lowered by 17.3% (95% CI 3.9–30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F₂-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Coenzyme Q and vitamin E need each other as antioxidants

Summary Both vitamin E and coenzyme Q possess distinct lipoprotective antioxidant properties in biological membranes. Their combined antioxidant activity, however, is markedly synergistic when both are present together. While it is likely that vitamin E represents the initial chain-breaking antioxidant during lipid peroxidation, both fully reduced CoQH₂ (ubiquinol) and semireduced CoQH^. (ubisemiquinone) appear to efficiently recycle the resultant vitamin E phenoxyl radical back to its biologically active reduced form. We describe and support a potential kinetic mechanism whereby vitamin E and coenzyme Q interact in such a way as to usurp the prooxidant effects of O ₂ ^−. . Physical interactions of vitamin E and coenzyme Q within the environment of the membrane lipid bilayer facilitate the recycling of vitamin E by ubisemiquinone and ubiquinol. Lastly, data are linked into a catalytic cycle that serves to connect normal electron transport mechanisms within biological membranes to the maintenance of lipoprotective antioxidant mechanisms.     

Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence

Multiple reactive oxygen/nitrogen species induce oxidative stress. Mammals have evolved with an elaborate defense network against oxidative stress, in which multiple antioxidant compounds and enzymes with different functions exert their respective roles. Radical scavenging is one of the essential roles of antioxidants and vitamin E is the most abundant and important lipophilic radical-scavenging antioxidant in vivo. The kinetic data and physiological molar ratio of vitamin E to substrates show that the peroxyl radicals are the only radicals that vitamin E can scavenge to break chain propagation efficiently and that vitamin E is unable to act as a potent scavenger of hydroxyl, alkoxyl, nitrogen dioxide, and thiyl radicals in vivo. The preventive effect of vitamin E against the oxidation mediated by nonradical oxidants such as hypochlorite, singlet oxygen, ozone, and enzymes may be limited in vivo. The synergistic interaction of vitamin E and vitamin C is effective for enhancing the antioxidant capacity of vitamin E. The in vitro and in vivo evidence of the function of vitamin E as a peroxyl radical-scavenging antioxidant and inhibitor of lipid peroxidation is presented.     

Membrane permeability changes with vitamin A/vitamin E mixed bilayers

Vitamin A (all trans-retinol) enhances the permeability of egg phosphatidylcholine liposomes to glucose, urea, and erythritol while vitamin E (α-tocopherol) decreases permeability to the same solutes. Egg phosphatidylcholine bilayers containing both vitamin A and vitamin E are shown to have an altered permeability more similar to that affected by vitamin E alone. The membrane stabilizing effect of vitamin E appears dominant over the membrane destabilizing effect of vitamin A.     

Synergistic inhibition of oxidation in dispersed phosphatidylcholine liposomes by a combination of vitamin E and cysteine

Oxidations of soybean phosphatidylcholine liposomes in an aqueous dispersion initiated by free radicals generated initially either in the aqueous phase or in the lipid phase were efficiently suppressed by vitamin E in the membranes. Vitamin E was consumed linearly with time and, when the inhibition period was over the oxidation proceeded rapidly at a rate similar to that in the absence of vitamin E. L-Cysteine was also effective by itself in scavenging radicals in the aqueous region, but it was consumed more rapidly than vitamin E. On the other hand, cysteine could not scavenge the radicals efficiently in a lipid region. Nevertheless, when vitamin E was incorporated into liposomes, the addition of cysteine in the aqueous phase prolonged the inhibition period and it reduced the rate of decay of vitamin E markedly even when the radicals were generated initially in the lipid bilayer. Furthermore, it was found by an electron spin resonance study that chromanoxyl radical disappeared quite rapidly when it was mixed with cysteine and that the spin adduct of cysteine radical was observed in the presence of alpha-(4-pyridyl-N-oxide)-N-tert-butyl nitrone. It was concluded that L-cysteine located in an aqueous region could regenerate vitamin E by reacting with vitamin E radical formed in a lipid region and show a synergistic antioxidant effect, although its efficiency of vitamin E regeneration was lower than that by vitamin C.     

Stopped-flow investigation of the reaction between vitamin E radical and vitamin C in solution

Kinetic study of the reaction between vitamin E radical and vitamin C has been performed. The rates of reaction of vitamin C (ascorbic acid 1, 6-0-stearyl ascorbic acid 2, and 2,6-O-dipalmitoyl ascorbic acid 3) with vitamin E radical (5,7-diisopropyl-tocopheroxyl) in benzene-ethanol (2:1, v/v) solution have been determined spectrophotometrically, using stopped-flow technique. The second-order rate constants obtained are 549 +/- 30 M-1s-1 for 1, 626 +/- 53 M-1s-1 for 2, and 4.84 +/- 1.41 M-1s-1 for 3 at 25.0 degrees C. The result shows that the ascorbic acid ester 2 having a long-alkyl-chain at 6-position is 1.14 times as reactive as the ascorbic acid 1, whereas the ascorbic acid ester 3 substituted at 2-position is only 0.01 times as reactive as the ascorbic acid 1.     

Influence of dietary vitamin E and C supplementation on vitamin E and C content and thiobarbituric acid reactive substances (TBARS) in different tissues of growing pigs

To investigate the influence and possible interactions of dietary vitamin E and C supplementation on vitamin content of both vitamins and oxidative stability of different pork tissues 40 Large White barrows from 25?kg to 106?kg were allocated to four different cereal based diets: Basal diet (B), dl-α-tocopherylacetate?+?200?mg/kg (E), crystalline ascorbic acid?+?300?mg/kg (C) or both vitamins (EC). At slaughtering samples of liver, spleen, heart, kidney, backfat outer layer, ham and M. longissimus dorsi were obtained. Growth performance of the pigs and carcass characteristics were not influenced by feeding treatments. Dietary vitamin E supplementation had a significant effect on the vitamin E and α-tocopherol concentration in all investigated tissues. Backfat outer layer, liver, spleen, kidney and heart had higher vitamin E concentrations than ham and M. longissimus dorsi. Dietary vitamin C supplementation tended towards enhanced vitamin E levels except for ham samples. Therefore, some synergistic actions without dietary vitamin E supplementation between the two vitamins could be shown. The vitamin C concentration and TBARS were increased or at least equal in all tissues due to vitamin C supplementation. Dietary α-tocopherol supplementation resulted in lower TBARS in backfat outer layer (malondialdehyde 0.35?mg/kg in B vs. 0.28?mg/kg in E), but increased in heart and ham. When both vitamins were supplemented (EC) TBARS were lower in M. longissimus dorsi and backfat outer layer, equal in heart and higher in liver and ham compared to a single vitamin C supplementation. Rancimat induction time of backfat outer layer was 0.3?h higher in C compared to B and 0.17?h higher in EC than in E. Correlations between levels of both vitamins were positive for kidney (r?=?0.169), M. longissimus dorsi (r?=?0.499) and ham (r?=?0.361) and negative for heart (r?=???0.350). In liver and spleen no interaction could be found. In backfat outer layer vitamin E was positively correlated with rancimat induction time (r?=?0.550) and negatively with TBARS (r?=???0.202), but provided no evidence that dietary vitamin E supply led to better oxidative stability.     

Effect of vitamin C and E supplementation in modulating the peripheral nerve conduction following cold exposure in humans

Exposure to an extremely cold environment without proper protection leading to hypothermia is an emergency, one of the several complications of which is impairment in nerve conduction. Our previous work in the rat model has shown the beneficial effect of vitamin C in modulating the effect of hypothermia on nerve conduction. The present study aimed to evaluate the effect of vitamins C and E, administered alone or in combination, in modulating the effect of mild hypothermia on human ulnar nerve conduction. The study was carried out on 26 volunteers divided into three groups: group I received vitamin C supplementation (2000 mg/day in a single dose and 1,000 mg/day for the next 6 days), group II received vitamins C and E in combination (1,000 mg and 800 mg respectively in a single dose and 500 mg and 400 mg respectively for the next 6 days) and group III received vitamin E (800 mg in a single dose and the same for the next 6 days). The recordings were carried out before and after single and weekly supplementation in each group. There was a fall in ulnar nerve conduction velocity with a reduction in the oral temperature of 2–2.5 °C. Vitamin C administered alone and in combination with vitamin E reduced the fall in ulnar nerve conduction velocity. Prior supplementation with vitamin C and E could help ameliorate the impairment in human ulnar nerve conduction due to hypothermia.     

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.     

Modulation of signal transduction by vitamin E

The ability of vitamin E to modulate signal transduction and gene expression has been observed in numerous studies; however, the detailed molecular mechanisms involved are often not clear. The eight natural vitamin E analogues and synthetic derivatives affect signal transduction with different potency, possibly reflecting their different ability to interact with specific proteins. Vitamin E modulates the activity of several enzymes involved in signal transduction, such as protein kinase C, protein kinase B, protein tyrosine kinases, 5-, 12-, and 15-lipoxygenases, cyclooxygenase-2, phospholipase A2, protein phosphatase 2A, protein tyrosine phosphatase, and diacylglycerol kinase. Activation of some these enzymes after stimulation of cell surface receptors with growth factors or cytokines can be normalized by vitamin E. At the molecular level, the translocation of several of these enzymes to the plasma membrane is affected by vitamin E, suggesting that the modulation of protein-membrane interactions may be a common theme for vitamin E action. In this review the main effects of vitamin E on enzymes involved in signal transduction are summarized and the possible mechanisms leading to enzyme modulation evaluated. The elucidation of the molecular and cellular events affected by vitamin E could reveal novel strategies and molecular targets for developing similarly acting compounds.     

Molecular action of vitamin E in lipoprotein oxidation: implications for atherosclerosis

The oxidation theory of atherosclerosis proposes that the oxidative modification of low-density lipoproteins (LDL) plays a central role in the disease. Although a direct causative role of LDL oxidation for atherogenesis has not been established, oxidized lipoproteins are detected in atherosclerotic lesions, and in vitro oxidized LDL exhibits putative pro-atherogenic activities. alpha-Tocopherol (alpha-TOH; vitamin E), the major lipid-soluble antioxidant present in lipoproteins, is thought to be antiatherogenic. However, results of vitamin E interventions on atherosclerosis in experimental animals and cardiovascular disease in humans have been inconclusive. Also, recent mechanistic studies demonstrate that the role of alpha-TOH during the early stages of lipoprotein lipid peroxidation is complex and that the vitamin does not act as a chain-breaking antioxidant. In the absence of co-antioxidants, compounds capable of reducing the alpha-TOH radical and exporting the radical from the lipoprotein particle, alpha-TOH exhibits anti- or pro-oxidant activity for lipoprotein lipids depending on the degree of radical flux and reactivity of the oxidant. The model of tocopherol-mediated peroxidation (TMP) explains the complex molecular action of alpha-TOH during lipoprotein lipid peroxidation and antioxidation. This article outlines the salient features of TMP, comments on whether TMP is relevant for in vivo lipoprotein lipid oxidation, and discusses how co-antioxidants may be required to attenuate lipoprotein lipid oxidation in vivo and perhaps atherosclerosis.     

Kinetic study of the reaction between vitamin E radical and alkyl hydroperoxides in solution

Kinetic study of the reaction between vitamin E radical and alkyl hydroperoxides has been performed, as a model for the reactions of lipid hydroperoxides with vitamin E radical in biological systems. The rates of reaction of hydroperoxides (n-butyl hydroperoxide 1, sec-butyl hydroperoxide 2, and tert-butyl hydroperoxide 3) with vitamin E radical (5,7-diisopropyl-tocopheroxyl 4) in benzene solution have been determined spectrophotometrically. The second-order rate constants, k-1, obtained are 1.34 x 10(-1) M-1s-1 for 1, 2.42 x 10(-1) M-1s-1 for 2, and 3.65 x 10(-1) M-1s-1 for 3 at 25.0 degrees C. The result indicates that the rate constants increase as the total electron donating capacity of the alkyl substituents at alpha-carbon atom of hydroperoxides increases. The above rates, k-1, are about seven order of magnitude lower than those, k1, for the reaction of vitamin E with peroxyl radical.     

Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin A dimers in wild-type rodents

Degenerative eye diseases are the most common causes of untreatable blindness. Accumulation of lipofuscin (granular deposits) in the retinal pigment epithelium (RPE) is a hallmark of major degenerative eye diseases such as Stargardt disease, Best disease, and age-related macular degeneration. The intrinsic reactivity of vitamin A leads to its dimerization and to the formation of pigments such as A2E, and is believed to play a key role in the formation of ocular lipofuscin. We sought a clinically pragmatic method to slow vitamin A dimerization as a means to elucidate the pathogenesis of macular degenerations and to develop a therapeutic intervention. We prepared vitamin A enriched with the stable isotope deuterium at carbon twenty (C20-D(3)-vitamin A). Results showed that dimerization of deuterium-enriched vitamin A was considerably slower than that of vitamin A at natural abundance as measured in vitro. Administration of C20-D(3)-vitamin A to wild-type rodents with no obvious genetic defects in vitamin A processing, slowed A2E biosynthesis. This study elucidates the mechanism of A2E biosynthesis and suggests that administration of C20-D(3)-vitamin A may be a viable, long-term approach to retard vitamin A dimerization and by extension, may slow lipofuscin deposition and the progression of common degenerative eye diseases.     

Perturbations in cerebral oxygen radical formation and membrane order following vitamin E deficiency

The effects of dietary vitamin E deficiency on mouse cerebral membrane order and oxygen reactive species were studied. Quantitation of vitamin E levels in several brain regions showed greatest deficiencies in striatum and cerebellum, followed by substantia nigra, and cortex. Vitamin E deficiency increased central-core membrane order in cerebral P2 fraction, but was without effect in the superficial hydrophilic membrane domain. Oxygen radical formation was studied using the probe 2',7'-dichlorofluorescein diacetate. Basal generation rates of oxygen reactive species were 2.5-fold higher when compared to control animals. While hepatic levels of vitamin E are much more reduced than brain levels, in deficient mice, the rate of oxygen radical formation in the liver was unaltered. This implies an special susceptibility of the brain to deficiency of this lipophilic antioxidant vitamin. Data demonstrate that endogenous levels of free radical scavengers, such as vitamin E, may play an important role in maintaining basal oxygen radical levels and membrane integrity. The dietary vitamin E depletion paradigm suggests that a relation exists between elevated levels of oxygen radicals and more rigid hydrophobic central-cores in cerebral membranes, effects that may play a role in mechanisms underlying the neuropathologic lesions observed following vitamin E deficiency.     

Mitochondrial respiratory chain dysfunction in ageing; influence of vitamin E deficiency

The causes and consequences of ageing are likely to be complex and involve the interaction of many processes. It has been proposed that the decline in mitochondrial function caused by the accumulation of oxidatively damaged molecules plays a significant role in the ageing process. In agreement with previous reports we have shown that the activities of NADH CoQ₁ reductase and cytochrome oxidase declined with increasing age in both rat liver and gastrocnemius muscle mitochondria. However, only in the liver were the changes in lipid peroxidation and membrane fluidity suggestive of an age-related increase in oxidative stress.

After 12 weeks on a vitamin E deficient diet, vitamin E levels were undetectable in both gastrocnemius muscle and liver. In skeletal muscle, this was associated with a statistically significant increase in lipid peroxidation, a decrease in cytochrome oxidase activity after 48 weeks, and an exacerbation in the age-related rate of decline of NADH CoQ₁ reductase activity. This was consistent with the suggestion that an imbalance between free radical generation and antioxidant defence may contribute to the mitochondrial dysfunction with age. In contrast to this, vitamin E deficiency in the liver caused a significant increase in mitochondrial respiratory chain activities with increasing age despite evidence of increased lipid peroxidation. Comparison of other features in these samples suggested vitamin E deficiency; did not have a significant impact upon mtDNA translation; induced a compensatory increase in glutathione levels in muscle, which was less marked in the liver, but probably most interestingly caused a significant decrease in the mitochondrial membrane fluidity in muscle but not in liver mitochondria.

These data suggest that while increased lipid peroxidation exacerbated the age-related decline in muscle respiratory chain function this relationship was not observed in liver. Consequently other factors are likely to be contributing to the age-related decline in mitochondrial function and specific stimuli may influence or even reverse these age-related effects as observed with vitamin E deficiency in the liver.