Polystyrene surface coated with vitamin E modulates human granulocyte adhesion and MMP-9 release

Vitamin E (Vit.E, alpha-tocopherol) is a natural biological antioxidant and antinflammatory agent, which protects cells from the effects of free radicals and inhibits inflammation. For such properties Vit.E has been used to improve the biocompatibility of materials such as cellulose membrane for hemodialysis. In this study granulocytes adhesion and activation have been studied after contact with normal cell culture grade polystyrene (PS) and Vit.E-coated polystyrene (Vit.E 0.1 and 0.3% (v/v)) using optical microscopy, flow cytometry and substrate zymography. Vit.E increased the number of adherent granulocytes both at 0.1% (11470 +/- 1064 cells/cm(2), P < 0.01) and 0.3% ( 13706 +/-818) cells/cm(2), P < 0.001) concentration compared to normal PS (5529+/-692 cells/cm(2)). The morphology of granulocytes adherent to Vit.E-PS appeared lightly altered and no differences have been observed in their respiratory burst compared to control granulocyte, while matrix metalloproteinase 9 or gelatinase B (MMP-9) release and activation were increased compared to the normal PS samples. Our data indicate that Vit.E-coated surface induced an increase in granulocytes adhesion and MMP-9 release in the absence of the typical oxidative stress, hallmark of granulocytes activation. A possible explanation of the phenomenon is that Vit.E modifies the surface protein adsorption thus increasing cell adhesion and in turn MMP-9 releasing.     

Effect of vitamin A treatment on superoxide dismutase-deficient yeast strains

Vitamin A (Vit A) is widely suggested to be protective against oxidative stress. However, different studies have been demonstrated the pro-oxidant effects of retinoids in several experimental models. In this work, we used the yeast Saccharomyces cerevisiae as a model organism to study the Vit A effects on superoxide dismutase (SOD)-deficient yeast strains. We report here that Vit A (10, 20 and 40 mg/ml) decreases the survival of exponentially growing yeast cells, especially in strains deficient in CuZnSOD (sod1Δ) and CuZnSOD/MnSOD (sod1Δsod2Δ). We also observed the protective effect of vitamin E against the Vit A-induced toxicity. Possible adaptation effects induced by sub-lethal oxidative stress were monitored by pre-, co- and post-treatment with the oxidative agent paraquat. The enzymatic activities of catalase (CAT) and glutathione peroxidase (GPx), and the total glutathione content were determined after Vit A treatment. Our results showed that CuZnSOD represents an important defence against Vit A-generated oxidative damage. In SOD-deficient strains, the main defence against Vit A-produced reactive oxygen species (ROS) is GPx. However, the induction of GPx activity is not sufficient to prevent the Vit A-induced cell death in these mutants in exponential phase growth.     

Effect of cellular differentiation on cytokine-induced expression of human immunodeficiency virus in chronically infected promonocytic cells: dissociation of cellular differentiation and viral expression.

Cellular differentiation is thought to play an important role in the susceptibility of monocytic lineage cells to human immunodeficiency virus (HIV) infection as well as in their ability to support virus replication. In addition, virus replication in monocytes/macrophages has been demonstrated in vitro to be strongly modulated by several cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. The purpose of the present study was to investigate the interaction between cellular differentiation and cytokines in the regulation of HIV expression from chronically infected monocytic lineage cells. U1, a persistently HIV-infected promonocytic cell line, is characterized by low levels of virus expression which can be modulated by several cytokines. 1 alpha,-25-Dihydroxyvitamin D3 (Vit.D3), a well-known differentiating agent for myelomonocytic cells which has been previously reported to modulate HIV replication in other in vitro systems, induced maturation of U1 cells toward a macrophage-like phenotype, as demonstrated by the induction of the differentiation-associated cell surface markers CD14 and CD11b. Vit.D3-induced differentiation did not result in induction of HIV expression; however, when U1 cells were stimulated with tumor necrosis factor alpha in the presence of Vit.D3, a synergistic induction of cell differentiation and viral expression was demonstrated. In contrast, Vit.D3 suppressed the induction of HIV expression in U1 cells stimulated with gamma interferon, interleukin-6, and granulocyte-macrophage colony-stimulating factor, although synergy between Vit.D3 and these cytokines was observed in terms of cellular differentiation. These data suggest that differentiation of monocytic cells does not necessarily correlate with increased HIV expression.     

Vitamin E and regression of hypercholesterolemia-induced oxidative stress in kidney

Hypercholesterolemia (HC) is an independent risk factor for the onset and progression of renal disease. HC induces oxidative stress (OS) in the kidney; Vitamin E (Vit.E), an antioxidant, slows the progression of OS in the kidney. This study was to investigate if Vit.E regresses the HC-induced OS, and the regression is associated with an increase in the antioxidant reserve (AR). The studies were carried out in four groups of rabbits. The kidneys were removed under anesthesia. OS and AR in the renal tissue were assessed by measuring malondialdetyde (MDA) and chemiluminescent (CL) activity, respectively. High-cholesterol diet elevated the serum total cholesterol (TC), and the regular diet with or without Vit.E following a high-cholesterol diet reduced the serum TC to control levels. HC increased the MDA levels of kidney by 5.54-fold compared to control. The MDA contents of the kidneys in groups on regular diet with or without Vit.E were, respectively, 56 and 53 % lower than the control group. The CL activity in the control group was 12.15 ± 0.73 × 10⁶ RLU/mg protein. The CL activity in HC group was 45.26 % lower than that in control, indicating an increase in AR. The regular diet with or without Vit.E following high-cholesterol diet normalized the CL activity/AR. In conclusion, HC increases OS in the kidney; reduction of serum cholesterol by regular diet regresses the renal OS but Vit.E does not regress HC-induced OS in kidney.     

Effect of vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C

OBJECTIVES: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. METHODS: Seventeen HCV patients (male = 3; female = 14) of age 62 +/- 7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-alpha-tocopherol 500 mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients "T", low ALT group "L" (ALT < 70 IU/l) and high ALT group "H" (ALT > 70 IU/l), respectively. RESULTS: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p < 0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p < 0.0001) from the 1st to 3rd month in all three T, H and L groups. CONCLUSION: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels > 70 IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.     

Selenium and Vitamin E Deficiency in Pigs

The effect of selenium (Se) and vitamin E (Vit. E) on reproductive performance, growth and health was studied in pigs. Two levels of Se were used, 0.03 and 0.06 nag per kg feed. The major component of the experimental diets was barley originating from soil which had formerly produced crops with a very low content of Se. Prior to seeding, the area was divided into 2 plots, 1 of which was treated with Se in the form of sodium selenite, 100 g Se per ha. The use of Se enriched fertilizer was an effective way of increasing the Se concentration of the grain. Thus the concentration of Se in the barley produced on the treated area was 5 times higher than in barley from the untreated one. Vit. E was added at a level of 30 i.u. per kg feed, and the concentrations were approx. 15 and 45 i.u. in the basal and experimental diets, respectively. The higher level of Se or Vit. E was not significantly associated with milk yield of the sow, litter size, birth weight or haemoglobin levels. However, there was a tendency to an increase in milk yield of the sows following additions of Se plus Vit. E, and litter size was slightly higher from sows which had received an addition of Vit. E. The concentration of Se and Vit. E was much higher in colostrum than in sow milk, and additions of dietary Se and Vit. E were associated with marked increases in the concentrations of these compounds in both colostrum and sow milk. There was a moderately improving effect of a high Se concentration in feed on growth rate and feed utilization. Low dietary levels of Se and Vit. E were followed by increased mortality rate in piglets; iron toxicity in connection with iron treatment was observed in piglets on low dietary Vit. E. Symptoms characteristic of PSE were not observed in the Se and Vit. E deficient pigs.     

冷暴露小鼠尾动脉舒缩功能变化以及血管活性药物的作用特征

目的：研究不同温度条件下血管舒缩功能变化及哌唑嗪、山莨菪碱扩张血管作用变化特征,评价VitE在低温条件下的内皮保护作用,探讨上述药物在冻伤预防过程中的应用前景。方法：利用血管条技术,观察小鼠尾动脉血管在8℃、16℃、25℃、37℃四个温度条件下的收缩及舒张反应特点,比较哌唑嗪、山莨菪碱在不同温度条件下扩血管作用差异。在冷暴露处理的同时预敷Vit E,观察其对低温条件下血管内皮依赖性舒张功能的改善作用。结果：①不同温度条件下苯肾上腺素诱发的血管收缩反应存在明显差异,温度越低,收缩幅度越小;②硝普钠浓度依赖的扩血管作用随着温度的降低明显增强;③与硝普钠作用特点类似,哌唑嗪、山莨菪碱在低温条件下的扩血管作用强于37℃组;④低温能够降低乙酰胆碱内皮依赖的扩血管作用,Vit E能够剂量依赖地对抗低温的影响。结论：随着温度的降低,苯肾上腺素作用下的血管收缩明显减弱,平滑肌靶点扩血管药物的作用显著增强。乙酰胆碱内皮依赖的扩血管作用随温度的下降有所降低,Vit E能够在一定程度上减小低温对乙酰胆碱扩血管作用的影响。     

Optimization of Dexamethasone Mixed Nanomicellar Formulation

The purpose of this study was to develop a clear aqueous mixed nanomicellar formulation (MNF) of dexamethasone utilizing both d-α-tocopherol polyethylene glycol-1000 succinate (Vit E TPGS) and octoxynol-40 (Oc-40). In this study, Vit E TPGS and Oc-40 are independent variables. Formulations were prepared following solvent evaporation method. A three level full-factorial design was applied to optimize the formulation based on entrapment efficiency, size, and polydispersity index (PDI). A specific blend of Vit E TPGS and Oc-40 at a particular wt% ratio (4.5:2.0) produced excellent drug entrapment, loading, small mixed nanomicellar size and narrow PDI. Solubility of DEX in MNF is improved by ~6.3-fold relative to normal aqueous solubility. Critical micellar concentration (CMC) for blend of polymers (4.5:2.0) was found to be lower (0.012 wt%) than the individual polymers (Vit E TPGS (0.025 wt%) and Oc-40 (0.107 wt%)). No significant effect on mixed nanomicellar size and PDI with one-factor or multi-factor interactions was observed. Qualitative ¹H NMR studies confirmed absence of free drug in the outer aqueous MNF medium. MNF appeared to be highly stable. Cytotoxicity studies on rabbit primary corneal epithelial cells did not indicate any toxicity suggesting MNF of dexamethasone is safe and suitable for human topical ocular drops after further in vivo evaluations.KEY WORDS: aqueous mixed nanomicelles, characterization, critical micellar concentration (CMC), dexamethasone, experimental design     

Protective action of vitamins on the spermatogenesis in lead-treated Swiss mice

The protective action of vitamins C and E against lead acetate-induced reduced sperm count and sperm abnormalities in Swiss mice has been studied. Intraperitoneal injection of lead acetate (10mg/kg body weight) in the present study stimulates lipid peroxidation in the testicular tissue, indicated by a significant increase in malondialdehyde content in the experimental mice group. This is associated with an increased generation of noxious reactive oxygen species (ROS). Significantly reduced sperm count associated with increased sperm abnormality percentage in the lead-injected mice group compared to controls substantially proves the ongoing damaging effects of lead-induced ROS on developing germ cells. However, intraperitoneal administration of vitamin C (Vit C) at a concentration equivalent to the human therapeutic dose (10 mg/kg body weight) was able to minimize significantly the testicular malondialdehyde content with a concomitant increase in sperm count and significant decrease in the percentage of abnormal sperm population. Vitamin E (Vit E) (100 mg/kg body weight) treatment of a batch of lead-injected mice had a similar effect as Vit C but with a comparatively lower efficacy. On the other hand, coadministration of both vitamins (Vit C + Vit E) at the above mentioned doses to lead-treated mice led to the most significant decline in malondialdehyde content along with elevated sperm count and reduction in the percentage of abnormal sperm population. The protective action and the synergistic action of both vitamins (C and E) against lead-induced genotoxicity are discussed.     

The effects of selenium,vitamin E and their combination on the composition of fatty acids and proteins in Saccharomyces cerevisiae

The aim of our studies was to test the effect and role of vitamin E and selenium supplements on yeast cell. In this study, the effects of selenium (Se), vitamin E (Vit. E), and their combination (Se plus Vit. E) on the composition of fatty acids and proteins were examined in Saccharomyces cerevisiae strains WET136 and 522. S. cerevisiae cells were grown up in YEPD medium supplemented with Se, Vit. E or their combination. It was found that the level of stearic acid was increased in all supplemented groups (p<0·05; p<0·001). The content of saturated and unsaturated fatty acids was decreased (p<0·05; p<0·01; p<0·001) in Vit. E and Vit. E plus Se supplemented S. cerevisiae. On the other hand, Se alone caused an increase (p<0·001) in the saturated fatty acids but a decrease (p<0·05; p<0·001) in the unsaturated fatty acids. Total proteins in S. cerevisiae were significantly increased (p<0·001) by Vit. E supplement. There was no significant change observed in S. cerevisiae supplemented with Se. These findings indicate that membrane composition of S. cerevisiae is affected by both Vit. E and Se supplements. © 1997 John Wiley & Sons, Ltd.     

Effect of vitamin E supplementation on post-exercise plasma lipid peroxidation and blood antioxidant status in smokers: with special reference to haemoconcentration effect

The oxidative effects were investigated of exhausting exercise in smokers, and the possible protective role of 400 mg day(-1) vitamin E (Vit E) supplementation over a period of 28 days. The subjects exercised to exhaustion including concentric-eccentric contractions following maximal cycling. The haematocrit and haemoglobin, leucocyte (WBC), plasma lactic acid (La) and malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), serum Vit E and ceruloplasmin (CER) concentrations were measured pre and post exercise. Supplementation increased Vit E concentrations 28% and 31% in the controls and the smokers, respectively. Cigarette smoking and/or Vit E supplementation did not influence plasma lipid peroxidation or the antioxidant status at rest. Exercise caused significant haemoconcentration in all groups. When the post-exercise concentrations were adjusted for haemoconcentration, a significant elevation in La concentrations due to exercise was observed in all groups. Similarly, there were significant elevations in the adjusted WBC counts in all groups except the Vit E supplemented controls. The MDA concentrations on the other hand, when adjusted for haemoconcentration, did not exhibit any difference due to exercise. Exercise did not affect the GPx and CER activities either, while causing a SOD activity loss in all groups except the Vit E supplemented non-smokers. Serum Vit E concentrations diminished significantly in all groups after exercise. Post-exercise plasma MDA and blood antioxidant concentrations were not altered by smoking. The results would suggest that plasma volume changes should always be taken into account when assessing post-exercise plasma concentrations and that smoking and exercise do not have an additional collective effect on plasma lipid peroxidation and the dose of Vit E administered was insufficient to maintain the serum concentrations after exercise.     

The influence of inclusions of vitamin E and corn oil on semen traits of Japanese quail (Coturnix coturnix japonica)

Reported was an investigation of the effect of vitamin E (Vit.E) and corn oil on semen traits of male Japanese quail (Coturnix coturnix japonica). From 8 to 20 wk of age, birds were raised on corn-based diets supplemented with corn oil (0 and 3%) and Vit.E (National Research Council (NRC) recommended 25mg/kg/day/dry matter and 150 mg/kg/day/dry matter) in a 2×2 factorial manner. The diet was supplemented with corn oil and Vit.E (E2C2) which provided additional n-6 polyunsaturated fatty acids in the form of 20:4n-6 and 22:4n-6 in spermatozoa phospholipid. The left testes weights were increased (P<0.01) in groups that received Vit.E in the diet (3.95 and 4.12 g, respectively) (P=0.03) and combined testes weight was the greatest in E2C2 group (7.57g) (P=0.02). Semen volume increased throughout the experiment in the E2C2 group. E2C1 and E2C2 birds had the greatest (90.05% and 92.1%, respectively) live sperm percent by comparison with other groups. The susceptibility of semen to lipid peroxidation in vitro was increased in quail fed E1C1 and E1C2, but was reduced when 150 mg Vit.E kg/day/dry matter feed was provided in the diet. The amount of Vit.E in the seminal plasma of E1C1 and E1C2 groups was (P<0.01) less than that in the other two groups (E2C1 and E2C2). From this study, it may be concluded that increasing diet n-6/n-3 ratio can be beneficial for semen traits, however, this application increased sperm peroxidation sensitivity but it can be controlled by inclusion of antioxidant such as Vit.E (150 mg/kg/day/dry matter) to diet.     

Influence of antioxidative vitamins A, C and E on lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

Persistent oxidative stress is thought to play an important role in carcinogenesis. Vitamins may influence oxygen radical metabolism and thus inhibit tumor growth. In the present trial the effects of Vitamins (Vit.) A, C and E on neoplastic growth and lipid peroxidation in pancreatic tissue were evaluated on chemically-induced pancreatic adenocarcinoma in the Syrian hamster. The incidence of pancreatic cancer was decreased by Vit. A (64.3%) and Vit. C (71.4%) as compared to the control group (100%, P<0.05). All vitamins increased the activity of superoxidedismutase (SOD) in pancreatic carcinomas. Accumulation of vitamins in tumor cells seems to be responsible for high levels of SOD and consecutive intracellular increase of hydrogen peroxide levels. Since this effect is selectively toxic for tumor cells it might be one of the mechanisms decreasing the incidence of pancreatic cancer in our trial.     

Effect of Vitamin E on diabetes-induced changes in small intestine and plasma antioxidant capacity in rat

The present study was designed to evaluate the effect of Vitamin E (Vit. E) on diabetes-induced changes in small intestine, lipid peroxidation and plasma antioxidant capacity in rats. Twenty-four rats were divided into three groups (n=8), namely control, non-treated diabetic (NTD) and Vit. E-treated diabetic (VETD) groups. The VETD group received 300 mg of Vit. E daily in drinking water. After 6 weeks, the length and weight of small intestine, villus height, crypt depth and muscular layer thickness showed a significant increase in the NTD group compared to the control group. In the VETD group, these parameters did not show any significant difference compared to the control group. The level of malondialdehyde (MDA) in the red blood cells showed a significant increase in the NTD group, but not in the VETD group, compared to the control group. The plasma antioxidant capacity showed a significant increase in VETD compared to the NTD group. These findings indicate that Vit. E significantly improved small intestinal changes in diabetic rats and that these effects could be mediated at least in part by enhanced plasma antioxidant capacity and reduced lipid peroxidation.     

Vitamins C and E improve regrowth and reduce lipid peroxidation of blackberry shoot tips following cryopreservation

Oxidative processes involved in cryopreservation protocols may be responsible for the reduced viability of tissues after liquid nitrogen exposure. Antioxidants that counteract these reactions should improve recovery. This study focused on oxidative lipid injury and the effects of exogenous vitamin E (tocopherol, Vit E) and vitamin C (ascorbic acid, Vit C) treatments on regrowth at four critical steps of the plant vitrification solution number 2 (PVS2) vitrification cryopreservation technique; pretreatment, loading, rinsing, and regrowth. Initial experiments showed that Vit E at 11–15 mM significantly increased regrowth (P < 0.001) when added at any of the four steps. There was significantly more malondialdehyde (MDA), a lipid peroxidation product, at each of the steps than in fresh untreated shoot tips. Vit E uptake was assayed at each step and showed significantly more α- and γ-tocopherols in treated shoots than those without Vit E. Vit E added at each step significantly reduced MDA formation and improved shoot regrowth. Vit C (0.14–0.58 mM) also significantly improved regrowth of shoot tips at each step compared to the controls. Regrowth medium with high iron concentrations and Vit C decreased recovery. However, in iron-free medium, Vit C significantly improved recovery. Treatments with Vit E (11 mM) and Vit C (0.14 mM) combined were not significantly better than Vit C alone. We recommend adding Vit C (0.28 mM) to the pretreatment medium, the loading solution or the rinse solution in the PVS2 vitrification protocol. This is the first report of the application of vitamins for improving cryopreservation of plant tissues by minimizing oxidative damage.     

The detoxication of nitrate by two antioxidants or a probiotic,and the effects on blood and seminal plasma profiles and reproductive function of New Zealand White rabbit bucks

Forty-two New Zealand White male rabbits were housed individually in wire cages and randomly distributed among six experimental groups of seven rabbits each, during 16 to 61 weeks of age. There were three main nitrate groups: 0 (tap water), 350 and 700 ppm. Within the 700 ppm of nitrate, there were four subgroups, in which one group was used as control group and the other three groups were supplemented with either 200 ppm of ascorbic acid (vitamin (Vit) C), 200 ppm of Vit E with 0.2 ppm of selenium (Se) and 1000 ppm of probiotic. The nitrate was supplemented as a sodium nitrate. The aim is to test the ability of Vit C and Vit E, Se and probiotic on the deleterious effects (blood and seminal plasma biochemical constituents, semen quality and productive performance) of nitrate in drinking water. Rabbits given nitrate at 700 ppm had significantly lower plasma globulin, red blood cells (RBCs), hemoglobin (Hgb), packed cell volume % (PCV%) and total antioxidant capacity (TAC) than those given the other concentrations of nitrate. Vit C, Vit E with Se and probiotic resulted in significantly (P < 0.05) greater Hgb, RBCs, PCV% and TAC than those of bucks given water supplemented with only 700 ppm nitrate, but the aspartate aminotransferase and alanine aminotransferase concentrations in seminal plasma were lower. Testosterone in the blood plasma and the seminal plasma was significantly (P < 0.05) lower in rabbits given 700 ppm nitrate than in those given other concentrations of nitrate. Vit C, Vit E with Se and the probiotic significantly increased testosterone, fertility, number of offspring and total offspring weight of rabbits sired by bucks supplemented with 700 ppm of nitrate.     

L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress,Autophagy, and Apoptosis

Methamphetamine (METH)-induced cell death contributes to the pathogenesis of neurotoxicity; however, the relative roles of oxidative stress, apoptosis, and autophagy remain unclear. L-Ascorbate, also called vitamin (Vit.) C, confers partial protection against METH neurotoxicity via induction of heme oxygenase-1. We further investigated the role of Vit. C in METH-induced oxidative stress, apoptosis, and autophagy in cortical cells. Exposure to lower concentrations (0.1, 0.5, 1 mM) of METH had insignificant effects on ROS production, whereas cells exposed to 5 mM METH exhibited ROS production in a time-dependent manner. We confirmed METH-induced apoptosis (by nuclear morphology revealed by Hoechst 33258 staining and Western blot showing the protein levels of pro-caspase 3 and cleaved caspase 3) and autophagy (by Western blot showing the protein levels of Belin-1 and conversion of microtubule-associated light chain (LC)3-I to LC3-II and autophagosome staining by monodansylcadaverine). The apoptosis as revealed by cleaved caspase-3 expression marked an increase at 18 h after METH exposure while both autophagic markers, Beclin 1 and LC3-II, marked an increase in cells exposed to METH for 6 and 24 h, respectively. Treating cells with Vit. C 30 min before METH exposure time-dependently attenuated the production of ROS. Vitamin C also attenuated METH-induced Beclin 1 and LC3-II expression and METH toxicity. Treatment of cells with Vit. C before METH exposure attenuated the expression of cleaved caspase-3 and reduced the number of METH-induced apoptotic cells. We suggest that the protective effect of Vit. C against METH toxicity might be through attenuation of ROS production, autophagy, and apoptosis.     

Dietary supplementation of Vitamin E protects heart tissue from exercise-induced oxidant stress

Exhaustive endurance exercise in adult female albino rats (C-Ex) increased the generation of free radicals (R ·) in the myocardium, probably through enhanced oxidative mechanisms. Free radical mediated lipid peroxidation measured in the form of tissue MDA content also increased in C-Ex animals, suggesting the exercise-induced oxidative stress in these animals. Dietary supplementation of Vit E, for a period of 60 days significantly increased Vit E incorporation into the serum and myocardium, more so in the myocardium. Vit E supplementation to exercising animals completely abolished the radical production. The protection of Vit E against oxidative stress appears to be not mediated through the improvement of antioxidant mechanisms by enzymes like SOD, catalase and Se-GSH Px. However the non Se-GSH Px, the enzyme involved in the reduction of endoperoxides increased significantly in control and Vit E fed animals in response to exercise. The protection of Vit E against exercise-induced oxidative stress was correlated with its multivarious activities like a) scavenger of free radicals; b) inhibition of lipoxygenases; and c) reduction of peroxides in association with lipoxygenases. These studies indicate that dietary supplementation of Vit E protects the animals from the possible oxidative damages of endurance exercise.     

Dietary supplementation with vitamin E and C attenuates dexamethasone-induced glucose intolerance in rats

Glucocorticoid excess induces marked insulin resistance and glucose intolerance. A recent study has shown that antioxidants prevent dexamethasone (DEX)-induced insulin resistance in cultured adipocytes. The purpose of this investigation was to examine the effects of dietary vitamin E and C (Vit E/C) supplementation on DEX-induced glucose intolerance in rats. We hypothesized that feeding rats a diet supplemented with Vit E/C would improve glucose tolerance and restore insulin signaling in skeletal muscle, adipose, and liver and prevent alterations in AMPK signaling in these tissues. Male Wistar rats received either a control or Vit E/C-supplemented diet (0.5 g/kg diet each of L-ascorbate and DL-all rac-alpha-tocopherol) for 9 days prior to, and during, 5 days of daily DEX treatment (subcutaneous injections 0.8 mg/g body wt). DEX treatment resulted in increases in the glucose and insulin area under the curve (AUC) during an intraperitoneal glucose tolerance test. The glucose, but not insulin, AUC was lowered with Vit E/C supplementation. Improvements in glucose tolerance occurred independent of a restoration of PKB phosphorylation in tissues of rats stimulated with an intraperitoneal injection of insulin but were associated with increases in AMPK signaling in muscle and reductions in AMPK signaling and the expression of fatty acid oxidation enzymes in liver. There were no differences in mitochondrial enzymes in triceps muscles between groups. This study is the first to report that dietary Vit E/C supplementation can partially prevent DEX-induced glucose intolerance in rats.     

Induction of micronuclei by Zearalenone in Vero monkey kidney cells and in bone marrow cells of mice: protective effect of Vitamin E

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin mainly produced by Fusarium graminaerum, found as a world-wide contaminant mainly of corn and wheat. Previous studies have demonstrated that among several other effects on animals and humans, ZEN also displays hepatotoxicity, immunotoxicity and nephrotoxicity. ZEN is mainly known as a hormonal disrupter due to its estrogenic activities and consequent toxicity for reproduction. Furthermore, mutagenic and genotoxic proprieties of ZEN were disclosed recently, the molecular mechanisms of which are not yet well understood. In the present study, the genotoxic potential of ZEN was evaluated using genotoxicity tests: the 'cytokinesis block micronucleus assay' in Vero monkey kidney cells and the 'in vivo mouse bone marrow micronucleus assay'. In cultured cells treated with 5, 10 and 20 microM ZEN, the frequency of binucleated micronucleated cells (BNMN) was assessed in 1000 binucleated cells and in mice given oral doses of 10, 20 and 40 mg/kg bw, the frequency of polychromatic erythrocytes micronucleated (PCEMN) in bone marrow cells was assessed in 2000 polychromatic erythrocytes (PCE). The potential prevention of ZEN-induced effects by 25 microM Vitamin E (Vit E) was also evaluated.In vivo, doses of 10, 20 and 40 mg/kg bw ZEN representing, respectively 2, 4 and 8% of the LD50 (LD50 of ZEN in mice is 500 mg/kg bw), were administered to animals either with or without pre-treatment with Vit E (216.6 mg/kg bw) in order to evaluate its preventive potential.ZEN was found to induce micronuclei (MN) in a dose-dependent manner in cultured Vero cells as well as in mouse bone marrow cells. The present data emphasise the likely clastogenic pathway among the molecular mechanisms that underlay the ZEN-induced genotoxicity. Vit E was found to prevent partially-from 30 to 50%-these toxic effects, most likely acting either as a structural analogue of ZEN or as an antioxidant.