AZT induces oxidative damage to cardiac mitochondria: protective effect of vitamins C and E

AZT (zidovudine) is a potent inhibitor of HIV replication and a major antiretroviral drug used for AIDS treatment. A major limitation in the use of AZT is the occurrence of severe side effects. The aim of this work was to test whether AZT causes oxidative damage to heart mitochondria and whether this can be prevented by supranutritional doses of antioxidant vitamins. An experimental animal model was used in which mice were treated with AZT for 35 days (10 mg/kg/day) in drinking water. Animals treated with antioxidant vitamins were fed the same diet as controls but supplemented with vitamins C (ascorbic acid, 10 g/ kg diet) and E (alpha-dl-tocopherol, 0.6 g/kg diet) for 65 days before sacrifice. This resulted in a daily intake of 1250 mg/kg/day (vitamin C) and 75 mg/kg/day (vitamin E). Cardiac mitochondrial DNA (mtDNA) of mice treated with AZT had over 120% more oxo-dG (8-oxo-7,8-dihydro-2'-deoxyguanosine, which is a biomarker of oxidative damage to DNA) in their mitochondrial DNA than untreated controls. AZT treatment also caused an increase in mitochondrial lipid peroxidation and an oxidation of mitochondrial glutathione. Dietary supplementation with supranutritional doses of the antioxidant vitamins C and E protected against these signs of mitochondrial oxidative stress. The oxidative effects of AZT are probably due to an increase in production of reactive oxygen species by mitochondria of AZT-treated animals, raising the possibility that oxidative stress may play an important role in the cardiotoxicity of AZT.     

Antioxidant activity and metabolite profile of quercetin in vitamin-E-depleted rats

Dietary antioxidants interact in a dynamic fashion, including recycling and sparing one another, to decrease oxidative stress. Limited information is available regarding the interrelationships in vivo between quercetin and vitamin E. We investigated the antioxidant activity and metabolism of quercetin (Q) in 65 F-344 rats (n=13 per group) randomly assigned to the following vitamin E (VE)-replete and -deficient diets: (a) VE replete (30 mg alpha-tocopherol acetate/kg diet) control ad libitum (C-AL), (b) VE replete pair fed (C-PF), (c) VE replete+5.0 g Q/kg diet (R-VE+5Q), (d) VE deplete (<1 mg/kg total tocopherols)+5.0 g Q/kg diet (D-VE+5Q) and (e) D-VE. After 12 weeks, blood and tissue were collected for measurement of plasma vitamin E, quercetin and its metabolites, serum pyruvate kinase (PK), plasma protein carbonyls, malondialdehyde (MDA) and oxygen radical absorbance capacity. D-VE diets decreased serum alpha-tocopherol and increased PK activity in a time-dependent manner. The D-VE diet increased plasma protein carbonyls but did not affect MDA. Dietary quercetin supplementation increased quercetin and its metabolites in plasma and liver but did not affect D-VE-induced changes in plasma alpha-tocopherol, PK or protein carbonyls. Plasma isorhamnetin and its disposition in muscle were enhanced by the D-VE diet, as compared to the R-VE diet. Conversely, tamarixetin disposition in muscle was decreased by the D-VE diet. Thus, quercetin did not slow vitamin E decline in vivo; neither did it provide antioxidant activity in vitamin-E-depleted rats. However, vitamin E status appears to enhance the distribution of isorhamnetin into the circulation and its disposition in muscle.     

Hyperoxia-induced changes in antioxidant capacity and the effect of dietary antioxidants.

We investigated, by measuring oxygen radical absorbance capacity (ORAC), whether hyperoxia causes alterations in antioxidant status and whether these alterations could be modulated by dietary antioxidants. Rats were fed for 8 wk a control diet or a control diet supplemented with vitamin E (500 IU/kg) or with aqueous extracts (ORAC: 1.36 mmol Trolox equivalents/kg) from blueberries or spinach and then were exposed to air or >99% O2 for 48 h. Although the constituents of the extracts were not extensively characterized, HPLC indicated that blueberry extract was particularly rich in anthocyanins, and the spinach extract did not contain any anthocyanins. The ORAC was determined in samples without proteins [serum treated with perchloric acid (PCA); ORACPCA] and with proteins (ORACtot). Hyperoxia induced a decrease in serum protein concentration, an increase in serum ORACPCA, decreases in lung ORACPCA and ORACtot, and an equilibration of proteins and ORACPCA between serum and pleural effusion. These alterations suggested a redistribution of antioxidants between tissues and an increase in capillary permeability during hyperoxia. Only the blueberry extract was effective in alleviating the hyperoxia-induced redistribution of antioxidants between tissues.     

Dietary supplementation of pyrroloquinoline quinone disodium protects against oxidative stress and liver damage in laying hens fed an oxidized sunflower oil-added diet

The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na₂) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na₂; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na₂. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na₂ supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na₂ or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na₂ or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na₂ or vitamin E decreased the oxidized oil diet induced DNA tail length and tail moment to the basal levels in fresh oil diet. These results indicate that PQQ.Na₂ is a potential antioxidant and is as effective against oxidized oil-related liver injury in laying hens as vitamin E. The protective effects of PQQ.Na₂ against liver damage induced by oxidized oil may be partially due to its role in the scavenging of free radicals, inhibiting of lipid peroxidation and enhancing of antioxidant defense systems.     

Vitamin C - vitamin E interaction in juvenile lake sturgeon (Acipenser fulvescens R.), a fish able to synthesize ascorbic acid

The hypothesis that vitamin C interacts with vitamin E in vivo was investigated in juvenile lake sturgeon. Ten-month old lake sturgeon were fed diets supplemented with either 0 or 1250 mg ascorbic acid/kg diet concomitantly with either 0 or 200 mg α tocopherol/kg diet for 7 weeks at 17°C. Dietary vitamin C supplement resulted in significant increases of ascorbate concentrations in the posterior kidney and liver of sturgeon. Dietary vitamin E omission affected liver concentrations of α-tocopherol (10.0 ± 4.5 μg/g) in comparison to sturgeon fed a diet supplemented with vitamin E and vitamin C (99.5 ± 22.9 μg/g). Dietary vitamin C supplement decreased liver α-tocopherol concentration in vitamin E-deprived sturgeon. Also, vitamin E supplement lowered posterior kidney and liver ascorbic acid concentrations in vitamin C-deprived sturgeon. Gulonolactone oxidase and dehydroascorbic acid reductase activities were stimulated in groups fed vitamin C. Thiobarbituric acid-reactive substances concentrations (an indicator of lipid peroxidation) were higher in sturgeon fed either of vitamins as compared to sturgeon deprived of both vitamins. The results suggested that large doses of vitamins C and E may be prooxidant in vivo.     

Oxidative stress and antioxidant status in mouse kidney: effects of dietary lipid and vitamin E plus iron

The purpose of this study was to determine the effects of dietary fat, vitamin E, and iron on oxidative damage and antioxidant status in kidneys of mice. Sixty 1-month-old male Swiss-Webster mice were fed a basal vitamin E-deficient diet that contained either 8% fish oil + 2% corn oil or 10% lard with or without 1 g all-rac-alpha-tocopherol acetate or 0.74 g ferric citrate per kilogram of diet for 4 weeks. Significantly (P < 0.05) higher levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), and conjugated dienes were found in the kidneys of mice fed with fish oil compared with mice fed lard irrespective of vitamin E status. Mice maintained on a vitamin E-deficient diet had significantly higher renal levels of TBAR, but not conjugated dienes, than the supplemented group. Fish oil fed mice receiving vitamin E supplementation had lower levels of alpha-tocopherol than did mice in the lard fed group. Significantly higher levels of ascorbic acid were also found in the kidneys of mice fed with fish oil than were found in mice fed lard. The levels of protein carbonyls and glutathione (GSH), and activities of catalase, superoxide dismutase, selenium (Se)-GSH peroxidase, and non-Se-GSH peroxidase were not significantly altered by dietary fat or vitamin E. Dietary iron had no significant effect on any of the oxidative stress and antioxidant indices measured. The results obtained provide experimental evidence for the pro-oxidant effect of high fish oil intake in mouse kidney and suggest that dietary lipids play a key role in determining cellular susceptibility to oxidative stress.     

Effect of oat by-product antioxidants and vitamin E on the oxidative stability of pork from pigs fed diets supplemented with linseed oil

The aim of the experiment was to compare the antioxidative potential of an oat by-product with the effect of vitamin E on the oxidative stability of pork from pigs fed a diet enriched with linseed oil. Thirty-four crossbreed barrows were fed individually from 39 to 109 kg body weight (BW) on one of four diets: a control diet based on barley-triticale-soybean (Diet C), a diet containing an oat byproduct (Diet O), and the same diets supplemented with vitamin E (100 mg/kg diet) (Diets CE and OE, respectively). The oat by-product, comprising oat hulls and bran, was included at 10 and 20% in the grower and finisher diets, respectively. To Diets O and OE, refined rapeseed oil was added to equalise their energy content to Diets C and CE. Compared to Diets C and CE, the inclusion of the oat by-product in Diets O and OE increased the antioxidative capacity of water-soluble and lipid soluble compounds in these diets. Dietary treatment did not influence growth performance, slaughter value, longissimus dorsi (LD) muscle quality measured by nutrient contents, pH, drip loss or colour. Vitamin E supplementation increased the alpha-tocopherol concentration in serum and meat (p < 0.01), and decreased the formation of thiobarbituric acid reactive substances (TBARS) in the fresh and stored LD (p < 0.01). In addition, diets with the oat by-product increased serum alpha-tocopherol concentration (p < 0.01) and decreased the TBARS levels in the fresh and stored LD (p < 0.05), without increasing muscle alpha-tocopherol concentration. The obtained results indicate that the phenolic compounds present in oat by-products have a considerable antioxidant potential and a beneficial effect on the pig organism and oxidative stability of meat. However, dietary inclusion with the oat by-product was not as efficient as supplementation with vitamin E.     

Does Dietary vitamin E or C Decrease Egg Yolk Cholesterol?

An experiment was conducted to determine the effect of dietary vitamin E and C on serum metabolites, yolk cholesterol, egg quality, and performance of layer hens. One hundred sixty-eight commercial Hy-Line W-36 layer hens were randomly divided into seven groups and six replicates with four hens in each. Dietary treatments were introduced after the pre-experimental period (10 days) to adjust egg production. Treatments were levels of vitamin E or C (100, 200, and 400 mg/kg diet) supplementation to the basal diet for 4 weeks, whereas the control group received no supplementation. Egg production, egg weight, and feed consumption were recorded during the study. Shell thickness, Haugh unit score, yolk color, yolk weight, yolk cholesterol, and blood parameters were measured at the end of experiment. There was no significant effect of dietary vitamin E or C on hen performance. Egg yolk cholesterol concentrations decreased linearly by antioxidant vitamin supplementation (P?<?0.01). Egg yolk cholesterol reduction did not have any negative effect on egg production rate. Antioxidants, especially vitamin C, increased serum glucose concentration (P?<?0.05). Serum total cholesterol content did not change by vitamin supplementation but cholesterol in high-density lipoprotein (HDL-C) decreased and cholesterol in low-density lipoprotein (LDL-C) increased (P?<?0.05), as dietary vitamin E or C supplementation increased in diets. These results are in conflict with the previous hypothesis that antioxidants have a role in LDL-C removal from the blood or increasing HDL-C. Vitamin E was more effective than vitamin C in this case and if these results are confirmed by further studies, they may result to revision in researchers’ point of view about antioxidant especially in human medicine.     

In vivo antioxidant properties of vitamin e and chromium in cold-stressed Japanese quails

An experiment was conducted to determine if vitamin E (α-tocopherol acetate) and chromium (chromium picolinate, Cr Pic) supplementation attenuate the negative effects of cold stress on egg production, egg quality, serum metabolites, and antioxidant status in Japanese quails (Coturnix coturnix japonica). One hundred and fifty laying Japanese quails (50-day-old) were divided into five groups, 30 birds per group. The laying quails kept at 6°C for 12 h/d (08.00 p.m. to 08.00 a.m.) were fed either a basal diet (low temperature-basal diet, CS group) or the basal diet supplemented with either 400 μg of Cr/kg of diet (Cr group), 250 mg of α-tocopherol-acetate per kg of diet (Vit. E group) or 400 μg of Cr plus 250 mg of α-tocopherol-acetate per kg of diet (Vit. E + Cr group) while quails kept at 18°C were fed a basal diet (thermo-neutral-basal diet, TN group). Performance and egg quality were significantly reduced in CS group compared with TN group. Supplemental chromium and vitamin E significantly increased live weight change, egg production, and improved feed efficiency in cold-stressed laying hens compared with the group fed the basal diet at 6°C. Egg production and egg weight were also greater (P < 0.05) in each supplemental group compared with the CS group. However, a combination of vitamin E and chromium, rather than each separately, provided the greatest performance. Supplemental vitamin E and chromium also increased serum vitamin C and E but, decreased malondialdehyde (MDA) concentrations (P < 0.05); the combination of vitamin E and chromium resulted in the highest levels of serum vitamin C and E within the cold-stressed quails. Results of the present study indicate that combined antioxidant supplements increased performance, egg quality and serum antioxidant levels while lowering MDA in cold-stressed quails.     

Protection of Heme Proteins by Vitamin E, Selenium, and β-Carotene Against Oxidative Damage in Rat Heart, Kidney, Lung and Spleen

Effects of the combination of vitamin E, selenium, and β-carotene on oxidative damage to rat heart, kidney, lung, and spleen were studied by measurement of the production of oxidized heme proteins (OHP) during spontaneous and prooxidant-induced oxidation. Male SD rats were fed with a vitamin E and selenium deficient diet or a diet supplemented with vitamin E, selenium, and β-carotene, Homogenates of heart, kidney, lung, and spleen were incubated at 37°C with and without the presence of bromotrichloromethane (CBrCl₃). The diet supplemented with antioxidants showed a strong protective effect against oxidative damage to heme proteins during the early stages of both spontaneous and CBrCl₃-induced oxidation in contrast to the antioxidant deficient diet. Synergism of multiple antioxygenic nutrients against oxidative damage to various animal tissues is discussed.     

Dietary eicosapentaenoic acid prevents systemic immunosuppression in mice induced by UVB radiation.

Moison, R. M. W. and Beijersbergen van Henegouwen, G. M. J. Dietary Eicosapentaenoic Acid Prevents Systemic Immunosuppression in Mice Induced by UVB Radiation. Radiat. Res. 156, 36-44 (2001).Reactive oxygen species (ROS) contribute to the immunosuppression induced by UVB radiation. Omega-3 fatty acids in fish oil, e.g. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can modulate immunoresponsiveness, but because of their susceptibility to ROS-induced damage, they can also challenge the epidermal antioxidant defense system. The influence of dietary supplementation with different omega-3 fatty acids on systemic immunosuppression induced in mice by UVB radiation was studied using the contact hypersensitivity response to trinitrochlorobenzene. In an attempt to study the mechanisms involved, UVB-radiation-induced changes in epidermal antioxidant status were also studied. Mice received high-fat (25% w/w) diets enriched with either oleic acid (control diet), EPA, DHA, or EPA + DHA (MaxEPA). Immunosuppression induced by UVB radiation was 53% in mice fed the oleic acid diet and 69% in mice fed the DHA diet. In contrast, immunosuppression was only 4% and 24% in mice fed the EPA and MaxEPA diets, respectively. Increased lipid peroxidation and decreased vitamin E levels (P < 0.05) were found in unirradiated mice fed the MaxEPA and DHA diets. For all diets, exposure to UVB radiation increased lipid peroxidation (P < 0.05), but levels of glutathione (P < 0.05) and vitamin C (P > 0.05) decreased only in the mice given fish oil. UVB irradiation did not influence vitamin E levels. In conclusion, dietary EPA, but not DHA, protects against UVB-radiation-induced immunosuppression in mice. The degree of protection appears to be related to the amount of EPA incorporated and the ability of the epidermis to maintain an adequate antioxidant level after irradiation.     

Effects of dietary chromium and ascorbic acid supplementation on digestion of nutrients,serum antioxidant status,and mineral concentrations in laying hens reared at a low ambient temperature

This experiment was conducted to evaluate the effects of chromium (chromium picolinate, CrPic) and vitamin C (l-ascorbic acid) supplementation on the digestion of nutrients and serum concentration of some antioxidant vitamins and minerals of laying hens (Hy-Line) reared at a low ambient temperature (6.8°C). One hundred twenty laying hens (32 wk old) were divided into 4 groups, 30 hens per group. The laying hens were fed either a basal diet or the basal diet supplemented with either 400 μg of Cr/kg diet, 250 mg of l-ascorbic acid/kg diet, or 400 μg of Cr plus 250 mg l-ascorbic acid/kg diet. The digestibility of nutrients (DM, OM, CP, and EE) increased by the supplementation of chromium and vitamin C (p<0.05). Supplemental chromium and vitamin C also increased serum vitamin C and E but decreased malondialdehyde concentrations (p<0.05). Additionally, supplemental chromium and vitamin C caused an increase in the serum concentrations of Fe, Zn, Mn, and Cr (p<0.05) but a decrease in Cu concentration. The results of the present study showed that each dietary supplement influenced most of the parameters measured in a similar way. Also, a combination of the two supplements resulted in an additive effect, and supplementing a combination of vitamin C (250 mg/kg of diet) and chromium (400 μg Cr/kg diet) may offer a potential protective management practice in preventing cold-stress-related depression in the performance of laying hens.     

Increase in heart glutathione redox ratio and total antioxidant capacity and decrease in lipid peroxidation after vitamin e dietary supplementation in guinea pigs

Dietary treatment with three diets differing in vitamin E, Low E (15 mg of vitamin E/kg diet), Medium E (150 mg/kg), or High E (1,500 mg/kg), resulted in guinea pigs with low (but nondeficient), intermediate, or high heart a-tocopherol concentration. Neither the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and reductase, nor the nonenzymatic antioxidants, GSH, ascorbate, and uric acid were homeostatically depressed by increases in heart a-tocopherol. Protection from both enzymatic (NADPH dependent) and nonenzymatic (ascorbate-Fe²⁺) lipid peroxidation was strongly increased by vitamin E supplementation from Low to Medium E Whereas no additional gain was obtained from the Medium E to the High E group. The GSH/GSSG and GSH/total glutathione ratios increased as a function of the vitamin E dietary concentration closely resembling the shape of the dependence of heart a-tocopherol on dietary vitamin E. The results show the capacity of dietary vitamin E to increase the global antioxidant capacity of the heart and to improve the heart redox status in both the lipid and water-soluble compartments. This capacity occurred at levels six times higher than the minimum daily requirement of vitamin E, even in the presence of optimum dietary vitamin C concentrations and basal unstressed conditions. The need for vitamin E dietary supplementation seems specially important in this tissue due to the low constitutive levels of endogenous enzymatic and nonenzymatic antioxidants present of the mammalian heart in comparison with those of other internal organs.     

Effects of vitamin E and beta-carotene on sperm competitiveness

Sperm are particularly prone to oxidative damage because they generate reactive oxygen species (ROS), have a high polyunsaturated fat content and a reduced capacity to repair DNA damage. The dietary compounds vitamin E and beta-carotene are argued to have antioxidant properties that help to counter the damaging effects of excess ROS. Here in, we tested the post-copulatory consequences for male crickets (Teleogryllus oceanicus) of dietary intake of these two candidate antioxidants. During competitive fertilisation trials, vitamin E, but not beta-carotene, singularly enhanced sperm competitiveness. However, the diet combining a high vitamin E dose and beta-carotene produced males with the most competitive ejaculates, possibly due to the known ability of beta-carotene to recycle vitamin E. Our results provide support for the idea that these two common dietary compounds have interactive antioxidant properties in vivo, by affecting the outcomes of male reproductive success under competitive conditions.     

Vitamin E deficiency sensitizes alveolar type II cells for apoptosis

Pre-term neonates and neonates in general exhibit physiological vitamin E deficiency and are at increased risk for the development of acute lung diseases. Apoptosis is a major cause of acute lung damage in alveolar type II cells. In this paper, we evaluated the hypothesis that vitamin E deficiency predisposes alveolar type II cells to apoptosis. Therefore, we measured markers of apoptosis in alveolar type II cells isolated from control rats, vitamin E deficient rats and deficient rats that were re-fed a vitamin E-enriched diet. Bax and cytosolic cytochrome c increased, and the mitochondrial transmembrane potential and Hsp25 expression was reduced in vitamin E deficiency. Furthermore, increased DNA-fragmentation and numbers of early and late apoptotic cells were seen, but caspases 3 and 8 activities and expression of Fas, Bcl-2, Bcl-x and p53 remained unchanged. Vitamin E depletion did not change the GSH/GSSG ratio and the activities of antioxidant enzymes. Thus, vitamin E deficiency may induce a reversible pro-apoptotic response in lung cells and sensitise them for additional insult. In agreement with this hypothesis, we demonstrate that in vivo hyperoxia alone does not induce apoptosis in type II cells of control rats but reversibly increases DNA-fragmentation and numbers of early apoptotic type II cells in vitamin E-depleted cells.     

Dietary vitamin E supplementation affects tissue lipid peroxidation of hybrid tilapia,Oreochromis niloticus x O. aureus

A feeding trial was conducted to evaluate the effects of dietary vitamin E contents on the growth, ascorbate induced iron-catalyzed lipid peroxidation in post-mortem muscle and liver tissue, and Raman spectral changes in lens of juvenile hybrid tilapia (Oreochromis niloticus x O. aureus). Experimental fish were fed practical diets supplemented with 0, 50, 100, 200, 450 and 700 mg alpha-tocopheryl acetate/kg diet for 14 weeks. There was no significant difference in weight gain, feed conversion ratio and protein efficiency ratio among fish fed test diets (P>0.05). Protein content of fish fed diet containing the lowest vitamin E level was the lowest (P<0.05) among all groups. No difference was found in other body constituents among test fish (P>0.05). The thiobarbituric acid-reactive substances produced by iron-catalyzed lipid peroxidation in muscle and liver tissue of fish fed the diet without alpha-tocopheryl acetate supplementation were significantly (P<0.05) greater than those from fish fed diets containing higher levels of alpha-tocopheryl acetate. Dietary vitamin E supplementation increased the antioxidant capability of tilapia tissues against lipid peroxidation. Further, dietary vitamin E supplementation also influenced the lens cortical membrane structure of tilapia.     

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.     

Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes

Free radicals have been suggested to play a role in adriamycin-induced cardiomyopathy. Adriamycin-induced myocardial effects were examined in rats maintained on a vitamin E deficient diet. Animals were divided into four groups: I, control; II, adriamycin-treated; III, vitamin E deficient diet; IV, vitamin E deficient diet plus adriamycin treatment. Adriamycin-treated animals (groups II and IV) were given six injections (i.p.) over two weeks for producing a cumulative dose of 15 mg/kg. Animals in groups III and IV were placed on vitamin E deficient diet starting two weeks prior to the first injection of adriamycin or vehicle. Myocardial tissue analysis were performed on animals sacrificed 1 week after the last injection. Mortality was significantly higher in group IV which also showed doubling of myocardial malondialdehyde content relative to the non-adriamycin-treated vitamin E deficient group (III). Myocardial cell damage in group IV was characterized by separation of the external lamina, subsarcolemmal changes, mitochondrial swelling and myofibril dropout. Group II hearts showed only a mild dilation of the sarcotubules and swelling of the mitochondria. Total sialic acid content of the sarcolemma in groups II, III and IV was 55, 90 and 24% of the control values in group I. These data show a characteristic sarcolemmal injury produced by adriamycin in hearts of animals with reduced antioxidant capacity which is probably mediated by increased free radical activity as well as lipid peroxidation.     

Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress

This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl₄ and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride (CCl₄) (1 ml/kg/3days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day, i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter, changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH) content, hepatic superoxide dismutase (SOD) activity, and serum total antioxidant capacity (TAC) level were evaluated. In CCl₄-induced liver fibrosis, the efficacy order was melatonin > L-carnitine > vitamin E, while in STZ-induced diabetes, the efficacy order was vitamin E ≥ melatonin > L-carnitine. In conclusion, these data indicate that low dose of melatonin is more effective than high doses of vitamin E and L-carnitine in reducing hepatic oxidative stress induced by CCl₄ and diabetes. Moreover, the potent effect of vitamin E in ameliorating diabetes can be linked not only to the antioxidant actions, but also to the superior effect in reducing diabetes-induced hyperglycaemia. Meanwhile, potency of L-carnitine was nearly the same in CCl₄ and diabetes-induced liver damage.