Protective effect of vitamin E on spinal cord injury by compression and concurrent lipid peroxidation

Studies were made on the influence of vitamin E on the effects of compression injury of the spinal cord associated with ischemia in rats. The motor disturbance induced by spinal cord injury was greatly reduced by vitamin E supplementation. After injury, the spinal cord evoked potentials showed greater recovery of both amplitude and latency in the vitamin E-supplemented group than in the control group. Spinal cord blood flow was promptly restored and remained normal after injury in the vitamin E-supplemented group, but was significantly decreased from 3 h after injury in the control group. Thiobarbituric acid (TBA)—reactive substances in the spinal cord was immediately increased by compression injury in both groups, and after injury it persisted at a high value for 24 h in the control group, but decreased within 1 h in the vitamin E-supplemented group. Pathological examination of the spinal cord showed less damage, such as bleeding and edema, in the vitamin E-supplemented group than in the control group. Vitamin E may have protective effects on the spinal cord by inhibiting damage induced by lipid peroxidation and/or by sustaining the blood flow by maintaining the normal metabolism of arachidonic acid.     

Effects of long-term vitamin E deficiency and restoration on rat hepatic peroxisomes

Effects of vitamin E deficiency and its restoration on biochemical characteristics of hepatic peroxisomes were studied. Rats were maintained on the vitamin E-deficient diet for 25 weeks and then on a diet supplemented with vitamin E for 5 weeks. Blood hemolysis by hydrogen peroxide and lipid peroxidation in the liver increased markedly in vitamin E-deficient rats. The former returned to the control level after the resupplying of vitamin E, but the latter did not. Of liver peroxisomal enzymes, the activities of catalase, D-amino-acid oxidase and urate oxidase decreased in vitamin E-deficient rats. On the other hand, activities of fatty acyl-CoA oxidase and carnitine acetyltransferase increased significantly in vitamin E-deficient rats. All activities of these peroxisomal enzymes were restored to the control levels in vitamin E-supplemented rats. The activities of the mitochondrial, lysosomal and microsomal enzymes tested showed no apparent change except that the change of mitochondrial palmitoyltransferase was shown to be similar to that of peroxisomal fatty acid oxidation. These results were also supported by cell fractionation techniques. Following the methods of aqueous polymer two-phase systems, the characteristics of peroxisomal surface membranes altered in respect of their hydrophobicity, but not in respect of the surface charge of peroxisomal membranes. These results indicate that peroxisomal functions, especially those of the fatty acid oxidation system, change their activities more sensitively than other intracellular organelles in response to the condition of vitamin E deficiency.     

Effect of vitamin E on adjuvant arthritis in rats

Adjuvant arthritis was induced in rats fed a diet deficient in or supplemented with vitamin E, and its severity was scored according to the macroscopic findings of their legs, tails, and ears. The average score so obtained was higher in the vitamin E-deficient diet group than in the group of rats supplemented with vitamin E. Whereas the A/G ratio remained depressed in vitamin E-deficient rats, rats on a vitamin E-supplemented diet showed a fast recovery from A/G-ratio depression. The serum levels of beta-glucuronidase and acid phosphatase were elevated after administration of an adjuvant. The serum levels of these lysosomal enzymes showed a remarkable increase in rats fed a vitamin E-deficient diet, while the elevation in lysosomal enzyme levels in rats fed a vitamin E-supplemented diet was inhibited. The levels of thiobarbituric acid (TBA) reactants in the synovia were elevated at 2 weeks after exposure to the adjuvant and were decreased thereafter. In rats maintained on a diet supplemented with vitamin E, on the other hand, the increase in synovial level of TBA reactive substances was inhibited. These observations suggest that the aggravation of adjuvant arthritis may be associated with lipid peroxidation and that antioxidants, such as vitamin E, may be beneficial for arthritis.     

Modulation of Platelet thromboxane A2 and arterial prostacyclin by dietary vitamin E

Platelets from vitamin E-deficient and vitamin E-supplemented rats generate the same amount of thromboxane A2 (TxA2) when they are incubated with unesterified arachidonic acid. Platelets from vitamin E-deficient rats produced more TxA2 than platelets from vitamin E-supplemented rats when the platelets are challenged with collagen. Arterial tissue from vitamin E-deficient rats generates less prostacyclin (PGI2) than arterial tissue from vitamin E- supplemented rats. The vitamin E effect with arterial tissue is observed when the tissue is incubated with and without added unesterified arachidonic acid. These data show that arterial prostacyclin synthesis is diminished in vitamin E-deficient rats. Vitamin E, in vivo, inhibits platelet aggregation both by lowering platelet TxA2 and by raising arterial PGI2.     

Generation of prostacyclin-like substance and lipid peroxidation in vitamin E-deficient rats

Endogenous generation of prostacyclin (PGI₂)-like substance and lipid peroxidation were studied in the aorta of rats fed on vitamin E-deficient diet and/or vitamin E-supplemented one for 4 to 10 months after they were weaned at 4 weeks. PGI₂-like substance was produced by the incubation of the aortic ring in pH 9.0 borate-buffered saline and was estimated by comparison of its antiaggregatory activity with that produced by known amounts of synthetic PGI₂. Thiobarbituric acid-reacting substance (TBARS) was determined as an indicator of lipid peroxidation. The generation of PGI₂-like substance was significantly reduced in rats fed on vitamin E-deficient diet for 8 and 10 months as compared with that in the animals fed on vitamin E-supplemented one for the same period (p<0.001). Mean concentration of TBARS in the aortae of rats fed on vitamin E-deficient diet for 10 months was significantly higher than that of the animals fed on vitamin E-supplemented diet for the same feeding period (p<0.001). These alterations in the aortae of rats fed on vitamin E-deficient diet were corrected by feeding them on vitamin E-supplemented diet for subsequent 2 months.     

Influence of vitamin E on polyamine metabolism in ozone-exposed rat lungs

The influence of vitamin E (E) on lung polyamine metabolism of rats exposed to ozone (O3) was examined. Rats fed diets wither E-deficient or supplemented with 1000 IU E/kg were exposed to 0.5 +/- 0.05 ppm O3 or filtered room air continuously for 5 days. They were then sacrificed and their lungs were analyzed for biochemical changes. Lung E content was strongly associated with the dietary level, and increased (36%, P less than 0.05) after O3 exposure only in E-supplemented rats. Lung polyamine metabolism was not affected in the air-control rats by E level, but increased after O3 exposure in both dietary groups. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were elevated above air controls. However, the increases were significant only for E-deficient rats when compared to E-supplemented rats. After O3 exposure, putrescine increased significantly in both dietary groups; spermidine increased but was significantly higher only in the E-deficient group; and spermine remained unchanged in both dietary groups. Elevated E content of supplemented rat lungs after O3 exposure may represent its mobilization under oxidant stress. Increased polyamine metabolism of E-deficient rats suggests either a greater sensitivity to injury by O3 or a possible antioxidant function for polyamines compensating for E deficiency.     

Effects of dietary vitamin E and selenium on arginase activity in the liver, kidneys, and heart of rats treated with high doses of glucocorticoid

The effects of dietary intake of vitamin E and selenium on arginase activity in the liver, kidneys, and heart of rats treated with high doses of prednisolone were investigated. Rats were divided into five groups. Groups 3, 4, and 5 received a daily supplement in their drinking water of vitamin E, Se, and a combination of vitamin E and Se, respectively, for 30 days. For 3 days subsequently, the control group (group 1) was given a placebo, and the remaining four groups were injected intramuscularly with prednisolone. The tissue samples were collected from each group at 4, 8, 12, 24, and 48 h after the last administration of prednisolone. In the group treated with prednisolone alone, arginase activity in the liver was found to have increased at all the time periods, whereas it had decreased significantly in the heart at 48 h. Arginase activity in the kidneys was not affected by prednisolone. Compared to the control and prednisolone groups, arginase activity in the kidneys and heart of the vitamin E- and Se-supplemented groups was found to be significantly increased at all time periods, however, no difference was seen in the combination group. Arginase activity in the liver of the vitamin E-supplemented group was found to have decreased at all time periods, however, in the Se group compared to the prednisolone group it had reduced at 24 and 48 h only. In the combination group compared to the prednisolone group, liver arginase activity increased constantly up to 12 h returning to normal values at 48 h. Vitamin E and Se in combination may prevent the changes in arginase activity in various tissues caused by prednisolone.     

Modulation of platelet thromboxane A2 and arterial prostacyclin by dietary vitamin E

Platelets from vitamin E-deficient and vitamin E-supplemented rats generate the same amount fo thromboxane A₂ (TxA₂) when they are incubated with unesterified arachidonic acid. Platelets from vitamin E-deficient rats produce more TxA₂ than platelets from vitamin E-supplemented rats when the platelets are challenged with collagen. Arterial tissue from vitamin E-deficient rats generates less prostacyclin (PGI₂) than arterial tissue from vitamin E-supplemented rats. The vitamin E effect with arterial tissue is observed when the tissue is incubated with and without added unesterified arachidonic acid. These data show that arterial prostacyclin synthesis is diminished in vitamin E-deficient rats. Vitamin E, $\text{in}$$\text{vivo}$, inhibits platelet aggregation both by lowering platelet TxA₂ and by raising arterial PGI₂.     

Vitamin E deficiency and vitamin C supplements: exercise and mitochondrial oxidation

The effects of dietary antioxidant vitamins E and C on exercise endurance capacity and mitochondrial oxidation were investigated in rats. The endurance capacity of both vitamin E-deficient and vitamin C-supplemented, E-deficient rats was significantly (P less than 0.05) lower (38.1 and 33.6%, respectively) than control animals. Compared with the normal and vitamin E-deficient rats, there was a significant (P less than 0.05) increase in the concentration of vitamin C in blood and liver of the vitamin E-deficient, C-supplemented animals. Hence dietary vitamin C supplementation does not prevent the inhibition of exercise endurance capacity or increased hemolysis seen in vitamin E deficiency. The mitochondrial activities for the oxidation of palmitoyl carnitine and alpha-ketoglutarate were significantly (P less than 0.05) decreased by a single bout of exercise in brown adipose tissue but not in muscle, heart, or liver from vitamin C-supplemented, E-deficient groups of rats when compared with the activities in the tissue from the same group of rats killed at rest. Similar results were also seen in brown adipose tissue from vitamin E-deficient rats. The results suggest a tissue-specific role for vitamins E and C in substrate oxidation and show that the poor endurance capacity of vitamin E-deficient rats cannot be attributed to any changes in the mitochondrial activity in skeletal or cardiac muscles. It is also concluded that vitamin C supplementation, at least at the dose employed in the present study, cannot counteract the detrimental effects associated with vitamin E deficiency.     

Vitamin E affects cell death in adult rat dentate gyrus

We have previously reported the presence of dying cells in the granule cell layer (GCL) of adult rat dentate gyrus (DG), where neurogenesis occurs. In particular, we found that cell death in the GCL increased in vitamin E deficiency and decreased in vitamin E supplementation. These findings were regarded as related to changes in neurogenesis rate, which in turn was influenced by vitamin E availability; a neuroprotective effect of vitamin E on cell death was also proposed. In order to verify this latter hypothesis, we have studied cell death in all layers of DG in vitamin E-deficient and vitamin E-supplemented rats and in control rats at different ages, using TUNEL and nick translation techniques. The phenotype of TUNEL-positive cells was characterized and the existence of dying BrdU-positive cells was investigated. Dying cells with neuronal phenotype were observed throughout the DG in all experimental groups. The number of TUNEL-positive cells decreased from juvenile to adult age. A higher number of TUNEL-positive cells in vitamin E-deficient rats and a lower number in vitamin E-supplemented rats, with respect to age-matched controls, were found; moreover, in these groups, TUNEL-positive cells had a different percentage distribution in the different layers of the DG. Our results confirm the occurrence of cell death in DG, demonstrate that cell death affects neuronal cells and support the hypothesis that the effect of vitamin E on cell death is not related to neurogenesis.     

Dietary vitamins A and E influence retinyl ester composition and content of the retinal pigment epithelium

Experiments were conducted to determine the influence of dietary levels of vitamin A and alpha-tocopherol on the amounts and composition of retinyl esters in the retinal pigment epithelium of light-adapted albino rats. Groups of rats were fed diets containing alpha-tocopherol and either no retinyl palmitate, adequate retinyl palmitate, or excessive retinyl palmitate. Other groups of rats received diets lacking alpha-tocopherol and containing the same three levels of retinyl palmitate. Retinoic acid was added to diets lacking retinyl palmitate. After 27 weeks, the animals were light-adapted to achieve essentially total visual pigment bleaches, and the neural retinas and retinal pigment epithelium-eyecups were then dissected from each eye for vitamin A ester determinations. Almost all of the retinyl esters were found in the retinal pigment epithelium-eyecup portions of the eyes, mainly as retinyl palmitate and retinyl stearate. Maintaining rats on a vitamin A-deficient, retinoic acid-containing diet led to significant reductions in retinal pigment epithelial retinyl ester levels in rats fed both the vitamin E-supplemented and vitamin E-deficient diets; contrary to expectations, the effect of dietary vitamin A deficiency was more pronounced in the vitamin E-supplemented rats. Vitamin A deficiency in retinoic acid-maintained animals also led to significant reductions in retinyl palmitate-to-stearate ester ratios in the retinal pigment epithelia of both vitamin E-supplemented and vitamin E-deficient rats. Excessive dietary intake of vitamin A had little, if any, effect on retinal pigment epithelial retinyl ester content or composition. Vitamin E deficiency resulted in significant increases in retinal pigment epithelial retinyl palmitate content and in palmitate-to-stearate ester ratios in rats fed all three levels of vitamin A, but had little effect on retinal pigment epithelial retinyl stearate content. In other tissues, vitamin E deficiency has been shown to lower vitamin A levels, and it is widely accepted that this effect is due to autoxidative destruction of vitamin A. The increase in retinal pigment epithelial vitamin A ester levels in response to vitamin E deficiency indicates that vitamin E does not regulate vitamin A levels in this tissue primarily by acting as an antioxidant, but rather may act as an inhibitor of vitamin A uptake and/or storage. The effect of vitamin E on pigment epithelial vitamin A levels may be mediated by the vitamin E-induced change in retinyl palmitate-to-stearate ratios.     

The effect of dietary vitamin E and beta-carotene on oxidation processes in the rat testis

The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta-carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis.     

Impact of vitamin E supplement in standard laboratory animal diet on microvascular manifestation of ischemia/reperfusion injury

Aimed at improving animal fertility and health, diets for farm and laboratory animals have over the last few years been supplemented with increasing amounts of the antioxidant vitamin E. We now demonstrate by intravital microscopy that feeding hamsters with a vitamin E-supplemented “standard” rodent diet (60 ppm vitamin E) significantly reduces the microvascular manifestations of ischemia/reperfusion injury when compared to animals fed a nonsupplemented diet. Postischemic leukocyte adhesion to venular endothelium was reduced from 770 ± 204 cells/mm² at 24 h after reperfusion in control animals on the nonsupplemented diet to 403 ± 105 cells/mm² in animals on the “standard” rodent diet (means ± SD, N = 7 animals per group, p < 0.01). Animals on the nonsupplemented diet showed a dramatic loss of capillary perfusion density until 7 days after reperfusion (to 21 ± 13% of preischemic baseline values), whereas this loss was significantly attenuated (to 71 ± 12% of preischemic values, p < 0.01) in animals on the “standard” rodent diet. No difference in the extent of reperfusion injury was seen between animals on the “standard” rodent diet and animals on diets with substantially higher vitamin E supplements (300 ppm–30.000 ppm). Besides underscoring the benefit of vitamin E in reducing the extent of ischemia/reperfusion injury, this study raises the concern that vitamin E supplements in “standard” laboratory animal diets may have a far-reaching impact on biomedical research by jeopardizing established animal models of disease.     

Effect of dietary vitamin E on methyl ethyl ketone peroxide damage to microsomal cytochrome P-450 peroxidase

The effect of dietary vitamin E on in vivo and in vitro damage by methyl ethyl ketone peroxide (MEKP) to cytochrome P-450 and its associated enzymatic activity was studied. In vivo, MEKP damaged microsomal cytochrome P-450 and cytochrome P-450-mediated peroxidases in vitamin E-deficient rat liver. Dietary vitamin E treatment of rats protected the microsomal enzymes from peroxide damage. In vitro, the extent of MEKP inhibition was different for tetramethylphenylenediamine (TMPD)-peroxidase, NADH-peroxidase, and aminopyrine demethylase. In vitro addition of MEKP induced production of more thiobarbituric acid reacting substances (TBARS) in liver microsomes from vitamin E-deficient rats than from vitamin E-supplemented rats. When NADH and/or NADPH were supplied as reductants of MEKP, the inhibition of aminopyrine demethylase activity and the generation of TBARS by added MEKP were markedly reduced. In vivo, adequate levels of vitamin E and of NADH and NADPH are probably necessary to provide important protection to the endoplasmic reticulum during metabolism of toxic organic peroxides, such as MEKP.     

维生素E在青年和老年大鼠肾脏缺血/再灌注损伤中的作用

目的:探讨维生素E(VE)在青年和老年大鼠肾缺血/再灌注损伤(RI/RI)中的作用。方法:采用夹闭双侧肾动、静脉45min后恢复血流的方法制作RI/RI模型,测定血清中尿素氮(BUN)、肌酐(Scr)、丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、诱生型一氧化氮合酶(iNOS)浓度,免疫组化检测肾皮质热休克蛋白70(HSP70)表达。流式细胞术检测肾皮质细胞凋亡率。结果:缺血/再灌注(I/R)后BUN、Scr含量明显升高,老年I/R组MDA含量高于青年I/R组,SOD含量低于青年IR组,HSP70、NO以及肾皮质细胞凋亡率高于control组;VE可显著降低RI/RI大鼠BUN、Scr、MDA、iNOS水平,升高NO和SOD水平,增加HSP70的表达,降低肾皮质细胞凋亡率。结论:VE可通过促进肾组织HSP70的表达,增加NO和SOD水平,提高大鼠体内清除自由基的能力,从而对青、老年大鼠肾缺血/再灌注损伤(RI/RI)起到一定的保护作用。     

Vitamin E regulates mitochondrial hydrogen peroxide generation.

The mitochondrial electron transport system consumes more than 85% of all oxygen used by the cells, and up to 5% of the oxygen consumed by mitochondria is converted to superoxide, hydrogen peroxide, and other reactive oxygen species (ROS) under normal physiologic conditions. Disruption of mitochondrial ultrastructure is one of the earliest pathologic events during vitamin E depletion. The present studies were undertaken to test whether a direct link exists between vitamin E and the production of hydrogen peroxide in the mitochondria. In the first experiment, mice were fed a vitamin E-deficient or-sufficient diet for 15 weeks, after which the mitochondria from liver and skeletal muscle were isolated to determine the rates of hydrogen peroxide production. Deprivation of vitamin E resulted in an approximately 5-fold increase of mitochondrial hydrogen peroxide production in skeletal muscle and a 1-fold increase in liver when compared with the vitamin E-supplemented group. To determine whether vitamin E can dose-dependently influence the production of hydrogen peroxide, four groups of male and female rats were fed diets containing 0, 20, 200, or 2000 lU/kg vitamin E for 90 d. Results showed that dietary vitamin E dose-dependently attenuated hydrogen peroxide production in mitochondria isolated from liver and skeletal muscle of male and female rats. Female rats, however, were more profoundly affected by dietary vitamin E than male rats in the suppression of mitochondrial hydrogen peroxide production in both organs studied. These results showed that vitamin E can directly regulate hydrogen peroxide production in mitochondria and suggest that the overproduction of mitochondrial ROS is the first event leading to the tissue damage observed in vitamin E-deficiency syndromes. Data further suggested that by regulating mitochondrial production of ROS, vitamin E modulates the expression and activation of signal transduction pathways and other redox-sensitive biologic modifiers, and thereby delays or prevents degenerative tissue changes.     

Plasmodium yoelii: comparative antimalarial activities of dietary fish oils and fish oil concentrates in vitamin E-deficient mice

Feeding vitamin E-deficient diets containing either fish oils such as menhaden, salmon, or anchovy oil or fish oil concentrates based on n-3 ethyl esters or free fatty acids protected mice against Plasmodium yoelii as indicated by decreased parasitemia and improved survival. The fish oil concentrates depressed plasma tocopherol levels more strongly in vitamin E-supplemented mice than the menhaden oil. The free fatty acid concentrate appeared to suppress parasitemia in vitamin E-deficient mice better than the menhaden oil, although ultimate survival was similar in both groups. Dietary manipulation of host antioxidant status offers promise as a possible means of malaria control.     

Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation

Iron and aluminum complexes of nitrilotriacetic acid cause severe nephrotoxicity in Wistar rats. In addition, a high incidence of renal cell carcinoma is seen in ferric nitrilotriacetate-treated animals. The present study was performed to see if lipid peroxidation is involved in ferric nitrilotriacetate toxicity. Ferric nitrilotriacetate had more bleomycin-detectable 'free' iron than any ferric salt, while iron complexed with desferrioxamine or ferric chondroitin sulfate had none. The toxicity of ferric nitrilotriacetate in vivo was more pronounced in vitamin E-deficient rats. A thiobarbituric acid-reactive substance was present in the kidneys of vitamin E-deficient rats in amounts markedly elevated compared to vitamin E-sufficient, or vitamin E-supplemented rats. Non-complexed nitrilotriacetate or aluminum nitrilotriacetate did not produce any thiobarbituric acid-reactive substance in vitamin E-sufficient rats died by the 58th day of administration. We suggest that the iron-stimulated production of free radicals leading to lipid peroxidation is the major cause of ferric nitrilotriacetate-mediated renal toxicity. Vitamin E, a known scavenger of free radicals, is effective in protecting against this iron-induced toxicity.     

Vitamin D ameliorates hepatic ischemic/reperfusion injury in rats

Vitamin D, most commonly associated with the growth and remodeling of bone, has been shown to ameliorate ischemia/reperfusion injury (IRI) in some tissues, yet its underlying mechanism remains elusive. This study was designed to examine the protective effect of vitamin D, if any, against hepatic IRI in rats and the underlying mechanism involved. Adult female Wistar rats were randomly divided into control, sham-operated (sham), ischemia/reperfusion (I/R), and ischemic-reperfused vitamin D-treated (vit D) groups. Rats in the I/R and vit D groups were subjected to partial (70 %) hepatic ischemia for 45 min, followed by 1 h of reperfusion. Vitamin D was given to rats orally in a dose of 500 IU/kg daily for 2 weeks before being subjected to I/R. Markers of liver damage, oxidative stress, inflammation and apoptosis were evaluated. Hepatic morphology was also examined. Vit D-treated rats had significantly lower serum levels of alanine aminotransferase, aspartate aminotransferase, and γ glutamyl transferase compared to rats in the I/R group. Also, vit D-treated rats showed a significant decrease in malondialdehyde, interleukin-1 beta, interleukin-6, tumor necrosis factor-α, nuclear factor κB, B cell leukemia/lymphoma 2-associated X protein, cytochrome c, and caspase-3 levels, with higher levels of glutathione peroxidase and B cell lymphoma 2 protein levels in liver tissues compared to I/R rats. Histological examination showed less damaged liver tissues with amelioration of apoptotic signs in the vit D group compared to the I/R group. In conclusion, vitamin D supplementation ameliorates hepatic IRI mostly by alleviating the inflammatory-apoptotic response mediated by the oxidative reperfusion injury insult.     

The Effect of Vitamin E-Deficiency in Isolated Rat Heart on the Cellular Defence System Against Free Radicals During Normal Reperfusion After Hypoxic, Ischemic and Ca2+-Free Perfusion

We investigated whether vitamin E plays a role in the protection against potential free radical formation and related biochemical changes in hypoxic, ischemic and Ca²⁺-depleted rat heart upon normal reperfusion.

In the heart of normally fed rats a decrease in the activity of superoxide dismutase and the capacity of the glutathione system, factors of the cellular protective mechanisms against free radicals, occurred upon exposure to the above mentioned treatments. This decrease was not further enhanced if vitamin E-deficient rat hearts were treated. Vitamin E-deficiency, however, led to detectable peroxidation of lipids if Ca²⁺-depleted or hypoxic hearts were reperfused. Lipid peroxidation was measured as the formation of thiobarbituric acid reactive material, which is readily formed during this process. Reflow after ischemia did not induce lipid peroxidation either in normal or in vitamin E-deficient rat heart.

Since changes in Ca²⁺ -homeostasis are thought to be primarily responsible for the Ca²⁺-reperfusion injury, a role for Ca²⁺-ions in lipid peroxidative processes, either directly or indirectly, seems indicated. Furthermore the results imply that even a sharp and extensive decrease of reduced glutathione, as seen upon Ca²⁺ -repletion after a period of Ca²⁺ -depletion, does not necessarily induce peroxidation of lipids in heart tissue. Obviously, vitamin E is very important in the protection of cardiac membranes. Replenishment of the water-soluble protective factors in the heart seems, however, more important during above mentioned treatments, especially since repair of the vitamin E-free radical is dependent on water-soluble factors.