Vitamin E and neurodegenerative disorders associated with oxidative stress

Several neurodegenerative disorders are associated with oxidative stress that is manifested by lipid peroxidation, protein oxidation and other markers. Included in these disorders in which oxidative stress is thought to play an important role in their pathogenesis are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), tardive dyskinesia, Huntington's disease (HD), and multiple sclerosis. This review presents some of the chemistry of vitamin E as an antioxidant and summarizes studies in which vitamin E has been employed in these disorders and models thereof.     

Vitamin A deficiency increases hepcidin expression and oxidative stress in rat

ObjectiveThe interaction between vitamin A and iron status has been widely reported; however, the exact mechanism involved in this interaction has not been well characterized. The present study investigated the mechanism involved in tissue iron accumulation and changes in the oxidative status in vitamin A–deficient rats.MethodsRats were treated with a control diet, a vitamin A–deficient diet, or a vitamin A/iron-deficient diet for 57 d. The animals were sacrificed; the blood, liver, and spleen were collected for biochemical analysis. Analysis of variance or Mann-Whitney tests were used to compare groups and Pearson's or Spearman's tests to investigate the bivariate correlation.ResultsVitamin A deficiency increased liver hepcidin mRNA and iron spleen concentrations; however, iron deficiency in vitamin A–deficient rats deeply inhibits liver hepcidin mRNA expression and significantly increases divalent metal transporter-1 mRNA levels. Liver ferroportin and hereditary hemochromatosis gene mRNA levels did not change in either treatment. In the vitamin A–deficient groups, liver carbonyl protein increased, whereas catalase and glutathione S-transferase activities decreased, suggesting that vitamin A protects the liver against protein oxidation. A significant positive correlation was found between lipid oxidative damage and iron concentration in the liver and spleen (r = 0.611, P = 0.007; r = 0.558, P = 0.025, respectively).ConclusionThese results suggest that vitamin A maintains iron homeostasis by the modulation of liver hepcidin expression. The increase of lipid peroxidation in vitamin A deficiency seems to be iron dependent, whereas protein oxidation is not.     

Soy protein reduces paraquat-induced oxidative stress in rats

The effect of soy protein, soy isoflavones and saponins on paraquat (PQ)-induced oxidative stress was investigated in rats. Rats were fed experimental diets containing casein (CAS), soy protein (SPI), and casein with soy isoflavones and saponins (CAS + IS). The diets were supplemented or not with 0.025% paraquat (CAS + PQ, SPI + PQ, and CAS + IS + PQ). The protective effects of soy protein, soy isoflavones, and saponins on paraquat-induced oxidative stress were examined. Ingestion of soy protein generally mitigated the lung enlargement (P = 0.076), loss of body weight (P = 0.051) and oxidation of liver lipid (P = 0.043) and glutathione (P = 0.035) induced by paraquat, although soy isoflavones and saponins did not. To determine whether soy protein exerted its antioxidative effects by preventing paraquat absorption from digestive organs, rats were fed CAS or SPI diets and orally administered a 12.5 g/L paraquat solution. Plasma, urine, and fecal paraquat concentrations did not differ between the two groups, indicating that soy protein did not prevent paraquat absorption. The present study suggests that intake of soy protein itself, but not soy isoflavones and saponins, reduces paraquat-induced oxidative stress in rats, although this effect was not due to reduced absorption of paraquat from digestive organs.     

Vitamin E supplementation improves cell-mediated immunity and oxidative stress of Asian men and women

Vitamin E is an efficient antioxidant and a modulator of the immune system. Although racial differences in both baseline vitamin E level and immunologic subsets are known, no reliable data exist for the Asian population. Furthermore, the extent of the effect of alpha-tocopherol in protecting lymphocyte cells against oxidative stress and its association with cell-mediated immunity have not been elucidated. This study was undertaken to investigate the immunologic and antioxidant effects of vitamin E in healthy ethnic Chinese men and women. Volunteers < 35 y old (n = 26) were supplemented with 233 mg/d dl-alpha-tocopherol for 28 d. The in vitro proliferative response to phytohemagglutinin (PHA) or lipopolysaccharide (LPS) of T-lymphocytes was determined in the study group before and after vitamin E supplementation. Cell-mediated immunity subsets and hydrogen peroxide production in T-lymphocytes were investigated by flow cytometry. The oxidant-antioxidant balance in plasma and urine was studied by spectrophotometric and gas chromatography-mass selective detection methods. The antioxidant properties of vitamin E were established (P: < 0.01) by the elevation of plasma vitamin E, together with depression in both plasma malondialdehyde and urinary DNA adduct 8-hydroxy-2'-deoxyguanosine after supplementation. Our data suggest a specific requirement for vitamin E in total-T and T-helper cell proliferation. We present the first evidence of the beneficial effects of supplemental vitamin E in healthy Chinese individuals on cell-mediated immunity and oxidative stress.     

Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats

Background and aims Lipid peroxidation is believed to be involved in the pathophysiology of a number of diseases and in the process of aging. This study investigates the effects of dietary supplementation with vitamin E (20 g/kg diet of all-rac-α-tocopheryl succinate for 3 weeks) on both non-enzymatic and enzymatic lipid peroxidation in experimental rats with carbon tetrachloride (CCl₄)-induced hepatotoxicity (2.5 mL/kg body). Methods Plasma, urine and liver samples from control rats (n = 6), CCl₄-treated rats (n = 6), and rats supplemented with vitamin E prior to CCl₄ treatment (n = 8) were collected. Non-enzymatic lipid peroxidation induced by free radicals was investigated by measurement of a major F₂-iso-prostane, 8-iso-prostaglandin F_2α (8-iso-PGF_2α). Cyclooxygenase-catalyzed enzymatic lipid peroxidation was measured with a major PGF_2α metabolite, 15-kto-13,14-dihydro-prostaglandin F_2α (15-K-DH-PGF_2α). Malondialdehyde and antioxidants in plasma were also quantified. Results CCl₄ treatment alone resulted in significantly higher levels of plasma, urinary and liver 8-iso-PGF_2α, and of plasma and urinary 15-K-DH-PGF_2α compared to controls. Rats supplemented with vitamin E prior to CCl₄ treatment had significantly lower levels of urinary and liver 8-iso-PGF_2α, urinary 15-K-DH-PGF_2α, and plasma malondialdehyde than rats treated with CCl₄ alone. However, plasma 8-iso-PGF_2α and plasma 15-K-DH-PGF_2α were not affected by vitamin E supplementation. Conclusion Thus, both non-enzymatic and enzymatic lipid peroxidation during experimental hepatic oxidative injury were suppressed by dietary vitamin E supplementation in rats. Received: 29 May 2000, Accepted: 16 November 2000     

Vitamin E supplementation protects erythrocyte membranes from oxidative stress in healthy Chinese middle-aged and elderly people

Elderly people are subject to higher levels of oxidative stress than are young people. Vitamin E, as a powerful antioxidant residing mainly in biomembranes, may provide effective protection against oxidative membrane damage and resultant age-related deterioration, especially in the elderly. We hypothesized that appropriate levels of vitamin E supplementation would protect erythrocyte membranes from oxidative stress and thus improve membrane fluidity in healthy middle-aged and elderly people. To test this, we conducted a 4-month double-blind, randomized trial in which 180 healthy subjects (55-70 years old) were randomly divided into 4 groups: group C (control), and 3 treatment groups in which daily doses of 100 mg (VE1), 200 mg (VE2), and 300 mg (VE3) dl-α-tocopheryl acetate were administered. We measured plasma α-tocopherol concentration, malondialdehyde, and superoxide dismutase levels, erythrocyte hemolysis, and erythrocyte membrane fluidity at the beginning and end of the trial. After 4 months supplementation, plasma α-tocopherol concentrations in the 3 treatment groups had increased by 71%, 78%, and 95%, respectively (all P < .01), and significant decreases in plasma malondialdehyde concentrations were observed in these groups (all P < .05). Erythrocyte hemolysis was decreased by 20% to 38% after vitamin E supplementation (all P < .05), and in addition, groups VE2 and VE3 showed dramatic improvements in erythrocyte membrane fluidity (P < .01). Surprisingly, superoxide dismutase activity also decreased significantly in the treatment groups (all P < .05). In summary, vitamin E supplementation apparently alleviates oxidative stress in healthy middle-aged to elderly people, at least in part by improving erythrocyte membrane fluidity and reducing erythrocyte hemolysis.     

Vitamin E does not modulate plasma lipid profile or C-reactive protein despite suppressing oxidative stress in orchiectomized rats

Vitamin E is known to improve antioxidant status and to prevent lipoprotein oxidation. However, the effect of vitamin E on other cardiovascular risk factors, including C-reactive protein (CRP) and lipid profile status, in orchiectomized rats is unknown. In the present study, 32 1-year-old male rats were randomized into two groups: a sham-control group (n = 8) and an orchiectomized group (n = 24). The orchiectomized group was divided into three groups of eight and assigned to one of the following treatments: orchiectomy (ORX), ORX + vitamin E mixture (65.6 mg/kg) diet, or ORX + vitamin E mixture (656 mg/kg) diet. For 120 days all four groups consumed a basal AIN-93M diet, while the vitamin E groups ate diets containing an additional vitamin E mixture. Four months after the study began, all the rats were killed, the blood was collected, and the plasma was assayed for antioxidant status, CRP, lipid profile, and indices of peroxidation. ORX decreased (P < .05) the plasma antioxidant status, superoxide dismutase (SOD) activity, and CRP level and increased (P < .05) the plasma malondialdeyde, nitrite, and lipid profile compared with that of the sham-control group. In contrast to the ORX group, supplementation with vitamin E mixture increased (P < .05) plasma antioxidant status and dose-dependently increased (P < .05) SOD activity, while the vitamin E decreased (P < .05) plasma malondialdeyde and nitrite. The vitamin E mixture had no effect on CRP or on lipid profiles when compared to the orchiectomized rats. In conclusion, vitamin E appears to reduce oxidative stress without modulating lipid profile or inflammatory response.     

Melatonin reduces oxidative stress induced by chronic exposure of microwave radiation from mobile phones in rat brain

PURPOSE: The aim of the study was to evaluate the intensity of oxidative stress in the brain of animals chronically exposed to mobile phones and potential protective effects of melatonin in reducing oxidative stress and brain injury. MATERIALS AND METHODS: Experiments were performed on Wistar rats exposed to microwave radiation during 20, 40 and 60 days. Four groups were formed: I group (control)- animals treated by saline, intraperitoneally (i.p.) applied daily during follow up, II group (Mel)- rats treated daily with melatonin (2 mg kg(-1) body weight i.p.), III group (MWs)- microwave exposed rats, IV group (MWs + Mel)- MWs exposed rats treated with melatonin (2 mg kg(-1) body weight i.p.). The microwave radiation was produced by a mobile test phone (SAR = 0.043-0.135 W/kg). RESULTS: A significant increase in the brain tissue malondialdehyde (MDA) and carbonyl group concentration was registered during exposure. Decreased activity of catalase (CAT) and increased activity of xanthine oxidase (XO) remained after 40 and 60 days of exposure to mobile phones. Melatonin treatment significantly prevented the increase in the MDA content and XO activity in the brain tissue after 40 days of exposure while it was unable to prevent the decrease of CAT activity and increase of carbonyl group contents. CONCLUSION: We demonstrated two important findings; that mobile phones caused oxidative damage biochemically by increasing the levels of MDA, carbonyl groups, XO activity and decreasing CAT activity; and that treatment with the melatonin significantly prevented oxidative damage in the brain.     

Multivitamin administration before ischemia reduces ischemia-reperfusion injury in rabbit skeletal muscle

This study investigated the effect of a multivitamin preparation administered before ischemia or before reperfusion, on ischemia-reperfusion (I/R) injury of skeletal muscle. An in vivo hindlimb skeletal muscle I/R model (2.5 h/2 h) was carried out on adult New Zealand white rabbits. Animals used as I/R models were treated with a multivitamin preparation (0.4 ml/kg bw i.v. bolus), containing alpha-tocopherol, ascorbic acid, retinol, vitamin B complex, 30 min before starting ischemia (group MV(isc)) or 5 min before reperfusion (group MV(rep)) and compared to animals with I/R without treatment (group IR) and sham operated animals (group SHAM). Interstitial edema (muscle interfiber area, %MIFA) and changes in microvessel size (microvessel cross sectional area, MVCSA, microm(2)) were measured. Plasma malondialdehyde concentrations (MDA-TBA, nmol/ml) served as a measure of lipid peroxidation. After 2h of reperfusion, ischemia-reperfusion developed a significant microvascular constriction and an interstitial edema (IR, vs SHAM;P< 0.01), but administration of antioxidative vitamins before the onset of ischemia reduced microvascular constriction and edema formation (P< 0.05 vs IR group). In a similar manner, administration of vitamins before ischemia lowered plasma MDA-TBA levels as compared to the untreated group during reperfusion (p< 0. 05). In animals treated with vitamins before reperfusion, the biochemical and morphological results showed no differences as compared to the untreated group.Antioxidative treatment with a multivitamin preparation exerted a beneficial effect on I/R injury of skeletal muscle when the aforementioned vitamins were administered before ischemia but not before the onset of reperfusion.     

Methanol-induced oxidative stress in rat lymphoid organs

Methanol is primarily metabolized by oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This paper reports data on the effect of methanol on antioxidant status and lipid peroxidation in lymphoid organs such as the spleen, thymus, lymph nodes and bone marrow of rats. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.w intraperitoneally) for detecting toxicity levels for one day, 15 d and 30 d, respectively. Administration of methanol at 15 and 30 d significantly (p<0.05) increased lipid peroxidation and decreased the enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (reduced glutathione and vitamin C) in lymphoid organs. However, lipid peroxidation and enzymatic and non-enzymatic antioxidants in the acute methanol exposed group animals were found to be significantly (p<0.05) increased. In one day methanol intoxication, the levels of free radicals initially increased, and to remove these free radicals, antioxidants levels were elevated, which generally prevented oxidative cell damage. But in longer periods of intoxication, when the generation of reactive free radicals overwhelmed the antioxidant defense, lipid peroxidation increased. Further, decreased antioxidants in 15 and 30 d methanol intoxication may have been due to overutilization of non-enzymatic and enzymatic antioxidants to scavenge the products of lipid peroxidation. In addition, the liver and kidney markers of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine significantly increased. This study concludes that exposure to methanol causes oxidative stress by altering the oxidant/antioxidant balance in lymphoid organs of the rat.     

2型糖尿病大鼠氧化应激介导肝脏和骨骼肌细胞内脂肪堆积的差异

目的观察2型糖尿病大鼠高脂饮食后肝脏和骨骼肌氧化应激及脂质堆积的差异。方法10只雄性Goto Kakisaki（GK）大鼠随机分为两组：糖尿病对照组和糖尿病硫辛酸治疗组（α-硫辛酸35mg／kg隔天腹腔内注射1次），健康Wistar大鼠4只为正常对照组，高脂饮食12周。测定各组大鼠肝、骨骼肌匀浆中的GSH、SOD和MDA及脂质谱水平，以及观察其组织病理形态学改变。结果糖尿病对照组肝组织GSH、SOD和MDA及脂质谱水平较正常对照组明显异常，经α-硫辛酸治疗后有明显改善，且GSH、SOD和MDA水平与甘油三酯水平相关；骨骼肌组织中除SOD外，GSH和MDA以及脂质谱水平在3组之间的变化，差异无统计学意义（P〉0．05）。糖尿病对照组有明显的肝细胞脂肪变性、坏死及炎性细胞浸润，硫辛酸治疗后有明显改善，而骨骼肌组织病理形态学无明显变化。结论12周高脂饮食可导致明显的氧化应激状态和细胞内脂肪堆积，但肝脏和骨骼肌两者之间存在一定差异，α-硫辛酸通过改善氧化应激状态而对细胞脂质代谢异常有明显的缓解作用。     

Supplementation of fenugreek leaves reduces oxidative stress in streptozotocin-induced diabetic rats

Trigonella foenum-graecum, commonly known as fenugreek, is a traditional medicinal plant of the Leguminoseae family in India. The antioxidant effect of fenugreek leaves was evaluated in the streptozotocin-induced diabetic rat model. The antioxidant effect was evaluated by estimating thiobarbituric acid-reactive substances and reduced glutathione and measuring the activities of catalase and superoxide dismutase in liver, heart, and kidney in diabetic rats. Fenugreek leaf powder supplementation significantly lowered lipid peroxidation and significantly increased the antioxidant system in diabetic rats. The effect at a dose of 1 g/kg of body weight of fenugreek leaf powder was similar to that of glibenclamide. Insulin restores all the parameters to near normal values. Thus, fenugreek leaf powder reduces oxidative stress in experimental diabetes.     

Vitamin E deficiency and prostaglandin synthesis in rat testes

A group of 8 weanling rats was fed a vitamin E(VE) deficient diet (D) and a control group was fed a VE sufficient diet (C) for 19 weeks. Levels of docosapentaenoic acid (22:5w6) in testis parenchyma lipids were significantly lower (p<0.05) in group D compared with group C. This decrease in 22:5w6, however, was not accompanied by the documented decrease in total testis weight of the VE deficient group. These results suggest that the 22:5w6 level in testis parenchyma lipids may be a sensitive indicator of VE deficiency in rats. There was no difference in the arachidonic acid (AA) level of testis parenchyma lipids between two groups. The tunica was the major site of prostaglandin (PG) synthesis in the testicular tissue and prostacyclin was the major PG synthesized from exogenous AA in the tunica. Both PGE₂ and 6-keto-PGF_1α derived from endogenous AA in tunica homogenate affer 30 min incubation appear to be greater in the control group than in the deficient group, although the difference was not statistically significant. These results imply that increased lipid peroxidation in VE deficiency can result in greater inactivation of PGH synthetase and thus can reduce the synthesis of PGs during the incubation.     

Panax ginseng reduces oxidative stress and restores antioxidant capacity in aged rats

Nutritional antioxidants interact with cells in an active mode, including retrieving and sparing one another, to diminish oxidative stress. However, the intracellular balance of prooxidants and antioxidants becomes unbalanced, favoring prooxidants during the aging process. One hypothesis is that an aging-associated increase in oxidative stress is the primary cause of aging. Hence, the research hypothesis for this study is that Korean red ginseng reduces oxidative stress in vivo. Therefore, we investigated the efficacy of Korean red ginseng water extract (GWE) in reducing aging-associated oxidative stress by measuring lipid peroxidation and antioxidant levels in older rats compared with young rats. We observed a significant increase in the markers for oxidative damage (eg, lipid peroxidation) and markers for vital organ damage (eg, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels) in aged rats. The oxidative damage was accompanied by a significant decrease in enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase, and nonenzymatic antioxidants such as reduced glutathione, vitamin E, and vitamin C. Aged rats fed a diet supplemented with Korean red ginseng water extract had significantly less oxidative damage, possibly by enhancing the enzymatic and nonenzymatic antioxidants status. Our data suggest that consumption of Korean red ginseng reduces lipid peroxidation and restores antioxidant capacity by suppressing oxidative stress in rats.