Protective Effect Of Α-tocopherol Research Articles

The Effect of α-Tocopherol on the Reduction of Inflammatory Processes and the Negative Effect of Acrylamide.

Our research aimed to show acrylamide’s influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA.

The Protective Effect of α-Tocopherol on the Content of Selected Elements in the Calvaria for Exposed Hens to TCDD in the Early Embryonic Period.

This paper focuses on negative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on element content in male chicken calvaria and α-tocopherol (vitamin E) ability to reduce its toxic potential on bone mineralization in offspring. In the experiment carried out once, a solution containing only DMSO, TCDD, TCDD + α-tocopherol, and exclusively α-tocopherol was administrated. Subsequently, on the 5th day after hatching, the mineral composition of the chicken calvaria was evaluated. The results obtained suggest that the use of α-tocopherol contributes to the maintenance of the concentration of calcium, magnesium, and manganese in the chicken calvaria treated with TCDD in the embryonic period. In turn, vitamin E increases the level of zinc. It has been found that α-tocopherol in chicken embryos has a protective effect against disturbance of level of chosen trace elements in the bones of offspring caused by the TCDD.

Hepatoprotective effects of vitamin E against hexachlorobenzene-induced hepatotoxicity and oxidative stress in rats: histological, biochimical and antioxidant status changes

The protective effects of α-Tocopherol (vitamin E) on liver injury induced by hexachlorobenzene (HCB) were investigated in adult male rats of Wistar strain. Animals were randomly divided into six groups of eight rats each. Group 1 and 2 have received HCB, dissolved in olive oil, at a dose of 4 mg or 16 mg/kg b.w., respectively. Group 3 and 4 were treated by the same doses of HCB (4 mg and 16 mg/kg b.w.) after 1 h of pretreatment with α-tocopherol at a dose of 100 mg kg−1 b.w. The other two groups served as controls; which received either olive oil only, a solvent of HCB, or α-tocopherol. A significant increase in hepatic lipid peroxidation (LPO) and GSH activity were observed following HCB administration. The activities of antioxidant enzymes like superoxide dismutase and catalase were significantly decreased while glutathione peroxidase was significantly increased following HCB administration. Similarly, a significant increase in plasma levels of various marker enzymes [aminotransferase (aspartate aminotransférase (AST) and alanine aminotransferase (ALT)), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and a decrease of total protein level were observed. Pretreatment with vitamin E of HCB treated rats ameliorated all biochemical parameters to near normal values. Liver histological study confirmed biochemical parameters and the beneficial role of vitamin E.

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells.

Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

Nitroxide free radicals protect macular carotenoids against chemical destruction (bleaching) during lipid peroxidation

Macular xanthophylls (MXs) lutein and zeaxanthin are dietary carotenoids that are selectively concentrated in the human eye retina, where they are thought to protect against age-related macular degeneration (AMD) by multiple mechanisms, including filtration of phototoxic blue light and quenching of singlet oxygen and triplet states of photosensitizers. These physical protective mechanisms require that MXs be in their intact structure. Here, we investigated the protection of the intact structure of zeaxanthin incorporated into model membranes subjected to oxidative modification by water- and/or membrane-soluble small nitroxide free radicals. Model membranes were formed from saturated, monounsaturated, and polyunsaturated phosphatidylcholines (PCs). Oxidative modification involved autoxidation, iron-mediated, and singlet oxygen-mediated lipid peroxidation. The extent of chemical destruction (bleaching) of zeaxanthin was evaluated from its absorption spectra and compared with the extent of lipid peroxidation evaluated using the thiobarbituric acid assay. Nitroxide free radicals with different polarity (membrane/water partition coefficients) were used. The extent of zeaxanthin bleaching increased with membrane unsaturation and correlated with the rate of PC oxidation. Protection of the intact structure of zeaxanthin by membrane-soluble nitroxides was much stronger than that by water-soluble nitroxides. The combination of zeaxanthin and lipid-soluble nitroxides exerted strong synergistic protection against singlet oxygen-induced lipid peroxidation. The synergistic effect may be explained in terms of protection of the intact zeaxanthin structure by effective scavenging of free radicals by nitroxides, therefore allowing zeaxanthin to quench the primary oxidant, singlet oxygen, effectively by the physical protective mechanism. The redox state of nitroxides was monitored using electron paramagnetic resonance spectroscopy. Both nitroxide free radicals and their reduced form, hydroxylamines, were equally effective. Obtained data were compared with the protective effects of α-tocopherol, which is the natural antioxidant and protector of MXs within the retina. The new strategies employed here to maintain the intact structure of MXs may enhance their protective potential against AMD.

Protective Effects of α-tocopherol on the Activity and Antioxidant Profile of Bovine Spermatozoa Subjected to Ferrous Ascorbate-Induced Oxidative Stress

As spermatozoa are highly vulnerable to oxidative stress development, in vitro antioxidants offer an additional line of defense to the male reproductive system against oxidative insults. α‑tocopherol (α-TOC) is the most abundant form of vitamin E identified in the seminal plasma and spermatozoa membranes, being able to terminate numerous oxidative chain reactions causing substantial damage to biomolecules vital for sperm survival. This study was designed to shed more light on the in vitro effects of α‑tocopherol with respect to the vitality and intracellular antioxidant profile of bovine spermatozoa subjected to ferrous ascorbate-induced oxidative stress. Spermatozoa were washed out from 50 bovine ejaculates, suspended in 2.9 % sodium citrate and subjected to α-TOC treatment (10, 50, 100 and 500 μmol/L) in the presence or absence of ferrous ascorbate (FeAA; 150 μmol/L FeSO4 and 750 μmol/L ascorbic acid) during a 6h in vitro culture. Spermatozoa motion parameters were assessed using the SpermVision™ computer-aided sperm analysis (CASA) system. Cell viability was examined with the metabolic activity (MTT) assay, and the nitroblue-tetrazolium (NBT) test was applied to quantify the intracellular superoxide formation. Cell lysates were prepared at the end of the experiments in order to assess the intracellular activity of superoxide dismutase (SOD), catalase (CAT), as well as glutathione (GSH) and malondialdehyde (MDA) concentrations. Treatment with FeAA reduced both spermatozoa motility parameters (P < 0.001) as well as viability (P < 0.05 with respect to Time 0 h; P < 0.01 in case of Time 2 h and P < 0.001 in relation to Time 6 h), decreased the antioxidant parameters of the samples (P < 0.001 in case of SOD; P < 0.01 with respect to CAT and GSH) but increased the superoxide production (P < 0.01 in case of Time 0h and P < 0.001 with respect to Times 2 h and 6 h) and lipid peroxidation (P < 0.001). α‑TOC administration resulted in a preservation of the spermatozoa motility characteristics (P < 0.001 with respect to 500 μmol/L α-TOC), viability (P < 0.001 in case of 500 μmol/L α-TOC and P < 0.05 with respect to 100 μmol/L α-TOC) and antioxidant profile (P < 0.01 related to the impact of 500 μmol/L α-TOC on the SOD activity; P < 0.05 in relation to CAT; P < 0.01 with respect GSH; 100-500 μmol/L α-TOC), with 500 μmol/L α-TOC being the most effective. Our results suggest that α‑tocopherol possesses significant antioxidant properties that may prevent the deleterious effects caused by free radicals to spermatozoa, and extend the fertilization potential of male reproductive cells.

Interplay between vitamin E and phosphorus availability in the control of longevity in Arabidopsis thaliana.

Vitamin E helps to control the cellular redox state by reacting with singlet oxygen and preventing the propagation of lipid peroxidation in thylakoid membranes. Both plant ageing and phosphorus deficiency can trigger accumulation of reactive oxygen species, leading to damage to the photosynthetic apparatus. This study investigates how phosphorus availability and vitamin E interact in the control of plant longevity in the short-lived annual Arabidopsis thaliana. The responses of tocopherol cyclase (VTE1)- and γ-tocopherol methyltransferase (VTE4)-null mutants to various levels of phosphorus availability was compared with that of wild-type plants. Longevity (time from germination to rosette death) and the time taken to pass through different developmental stages were determined, and measurements were taken of photosynthetic efficiency, pigment concentration, lipid peroxidation, vitamin E content and jasmonate content. The vte1 mutant showed accelerated senescence under control conditions, excess phosphorus and mild phosphorus deficiency, suggesting a delaying, protective effect of α-tocopherol during plant senescence. However, under severe phosphorus deficiency the lack of α-tocopherol paradoxically increased longevity in the vte1 mutant, while senescence was accelerated in wild-type plants. Reduced photoprotection in vitamin E-deficient mutants led to increased levels of defence chemicals (as indicated by jasmonate levels) under severe phosphorus starvation in the vte4 mutant and under excess phosphorus and mild phosphorus starvation in the vte1 mutant, indicating a trade-off between the capacity for photoprotection and the activation of chemical defences (jasmonate accumulation). Vitamin E increases plant longevity under control conditions and mild phosphorus starvation, but accelerates senescence under severe phosphorus limitation. Complex interactions are revealed between phosphorus availability, vitamin E and the potential to synthesize jasmonates, suggesting a trade-off between photoprotection and the activation of chemical defences in the plants.

Induction of oxiapoptophagy on 158N murine oligodendrocytes treated by 7-ketocholesterol-, 7β-hydroxycholesterol-, or 24(S)-hydroxycholesterol: Protective effects of α-tocopherol and docosahexaenoic acid (DHA; C22:6 n-3)

In demyelinating or non-demyelinating neurodegenerative diseases, increased levels of 7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC) and 24(S)-hydroxycholesterol (24S-OHC) can be observed in brain lesions. In 158N murine oligodendrocytes, 7KC triggers a complex mode of cell death defined as oxiapoptophagy, involving simultaneous oxidative stress, apoptosis and autophagy. In these cells, 7KC as well as 7β-OHC and 24S-OHC induce a decrease of cell proliferation evaluated by phase contrast microscopy, an alteration of mitochondrial activity quantified with the MTT test, an overproduction of reactive oxygen species revealed by staining with dihydroethidium and dihydrorhodamine 123, caspase-3 activation, PARP degradation, reduced expression of Bcl-2, and condensation and/or fragmentation of the nuclei which are typical criteria of oxidative stress and apoptosis. Moreover, 7KC, 7β-OHC and 24S-OHC promote conversion of microtubule-associated protein light chain 3 (LC3-I) to LC3-II which is a characteristic of autophagy. Consequently, 7β-OHC and 24S-OHC, similarly to 7KC, can be considered as potent inducers of oxiapoptophagy. Furthermore, the different cytotoxic effects associated with 7KC, 7β-OHC and 24S-OHC-induced oxiapoptophagy are attenuated by vitamin E (VitE, α-tocopherol) and DHA which enhances VitE protective effects. In 158N murine oligodendrocytes, our data support the concept that oxiapoptophagy, which can be inhibited by VitE and DHA, could be a particular mode of cell death elicited by cytotoxic oxysterols.

Physicochemical aspects of reaction of ozone with galactolipid and galactolipid-tocopherol layers.

The impact of reaction of galactolipids with ozone on the physicochemical properties of their monolayers was examined. In Megli and Russo (Biochim Biophys Acta, 1778:143–152, 2008), Cwiklik and Jungwirth (Chem Phys Lett, 486:99–103, 2010), Jurkiewicz et al. (Biochim Biophys Acta, 1818:2388–2402, 2012), Khabiri et al. (Chem Phys Lett, 519:93–99, 2012), and Conte et al. (Biochim Biophys Acta, 1828:510–517, 2013), the properties of layers formed from model mixtures composed of chosen lipids and selected oxidation products were studied, whereas in this work, question was raised as to how the oxidation reactions taking place in situ affect the physical properties of the galactolipid layers. So, set experiment should take into account the effect of all reaction products. The mechanical characteristics of monolayers of monogalactosyldiacyl-glycerol (MGDG) and digalactosyldiacylglycerol (DGDG) were determined by Langmuir trough technique, and the electrical properties of liposomes formed from these lipids by measuring their electrophoretic mobility. Considerable loss of galactolipid molecules forming monolayers was found at ozone concentrations (in aqueous medium) higher than 0.1 ppm with a stronger effect measured for MGDG. That goes along with the greater amounts of MDA found in the extracts of oxidized MGDG films compared with DGDG. Based on this, it was concluded that an additional galactose group present in DGDG molecules acts protectively under oxidative conditions. The surface tension of the solutions (of small volume) contacting the oxidized galactolipids films was significantly reduced, indicating the presence of soluble in polar media, surface active reaction products. The presence of α-tocopherol in mixtures with tested galactolipids at a molar ratio of lipid to tocopherol equal to 1.7:1 caused some inhibition of lipid oxidation, reducing the decrease of amount of lipid particles forming the monolayer. Here, also protective effect of α-tocopherol was greater for the MGDG compared to DGDG.

Histological and histometrical study of the protective role of α-tocopherol against sodium arsenite toxicity in rat ovaries.

This study examines histometrical changes induced by sodium arsenite (SA), as an environmental pollutant, and investigates the protective effect of α-tocopherol on ovaries of SA-treated rats during the prenatal stage until sexual maturity. Rats were classified into groups: control, SA (8 ppm/day), α-tocopherol (100 ppm/day), and SA+α-tocopherol. Treatment was performed from pregnancy until maturation when the rats and ovaries were weighed. The Cavalieri method was used to estimate volume of the ovaries, cortex, medulla, and corpus luteum. The mean diameter of oocytes, granulosa cells, and nuclei were measured and volume was estimated using the Nucleator method. The number of oocytes and thickness of the zona pellucida (ZP) were determined using an optical dissector and orthogonal intercept method, respectively. SA reduced the body and ovary weight, the number of secondary, antral and Graafian oocytes, volume of the ovaries, cortex, medulla and corpus luteum, mean diameter and volume of oocytes in primordial and primary follicles, mean diameter and volume of oocyte nuclei in all types of follicles, and mean thickness of the ZP in secondary and antral follicles. Also, the mean diameter and volume of granulosa cells and their nuclei in antral and Graafian follicles decreased significantly. Vacuolization and vascular congestion in the corpus luteum and an increase in the number of atretic oocytes were seen in the SA group. Most of these parameters were unchanged from the control level in the SA+α-tocopherol group. It was concluded that α-tocopherol supplementation reduced the toxic effects of SA exposure on ovarian tissue in rats.

Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Protection of Astaxanthin in Astaxanthin Nanodispersions Using Additional Antioxidants

The protective effects of α-tocopherol and ascorbic acid on astaxanthin in astaxanthin nanodispersions produced via a solvent-diffusion technique and stabilized by a three-component stabilizer system, were studied either individually or in combination by using response surface methodology. Generally, both α-tocopherol and ascorbic acid could retard the astaxanthin degradation in astaxanthin nanodispersions. The results showed that the using α-tocopherol and ascorbic acid can be more efficient in increasing the chemical stability of nanodispersions in comparison to using them individually. Using a response surface methodology (RSM) response optimizer, it was seen that addition of ascorbic acid (ascorbic acid/astaxanthin w/w) and α-tocopherol (α-tocopherol/astaxanthin w/w) in proportions of 0.4 and 0.6, respectively, would give the maximum chemical stability to the studied astaxanthin nanodispersions.

Protective Effects of α-Tocopherol and Ascorbic Acid against Cardol-Induced Cell Death and Reactive Oxygen Species Generation in Staphylococcus aureus

Cardol (C₁₅:₃), isolated from cashew (Anacardium occidentale L.) nut shell liquid, has been shown to exhibit bactericidal activity against various strains of Staphylococcus aureus, including methicillin-resistant strains. The maximum level of reactive oxygen species generation was detected at around the minimum bactericidal concentration of cardol, while reactive oxygen species production drastically decreased at doses above the minimum bactericidal concentration. The primary response for bactericidal activity around the bactericidal concentration was noted to primarily originate from oxidative stress such as intracellular reactive oxygen species generation. High doses of cardol (C₁₅:₃) were shown to induce leakage of K⁺ from S. aureus cells, which may be related to the decrease in reactive oxygen species. Antioxidants such as α-tocopherol and ascorbic acid restricted reactive oxygen species generation and restored cellular damage induced by the lipid. Cardol (C₁₅:₃) overdose probably disrupts the native membrane-associated function as it acts as a surfactant. The maximum antibacterial activity of cardols against S. aureus depends on their log P values (partition coefficient in octanol/water) and is related to their similarity to those of anacardic acids isolated from the same source.

α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities

The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H2O2-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H2O2-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3–18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H2O2 to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H2O2. Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H2O2-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H2O2-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H2O2 in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective.

Protective effects of α-tocopherol against oxidative stress related to nephrotoxicity by monosodium glutamate in rats

Context: Chronic oral intake of high doses of monosodium glutamate (MSG) could be harmful to tissues and organs. Oxidative stress enhances membrane damage by lipid peroxidation and alterations of antioxidant enzymes, which affects the functional activity of organs. Antioxidant vitamins have the capacity to regulate the oxidative stress related functional and pathological processes.Objective: In this study, the protective role of α-tocopherol against MSG-induced nephrotoxicity was analyzed. Materials and methods: MSG (4 g/kg) was given orally to female wistar rats for a period of 180 days. Renal function parameters (urea, uric acid, and creatinine), lipid peroxidation markers (malondialdehyde and conjugated dienes), antioxidant system (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, and reduced glutathione), and histopathology were investigated. All tests were done in rats treated with MSG and at two different doses of α-tocopherol (100 and 200 mg/kg).Results: Oral exposure of MSG significantly increased renal function markers, lipid peroxidation byproducts, and altered antioxidant system. Moreover, the kidney showed congested glomeruli, tubular swelling, capillary congestion and microhemorrhages in stromal areas of the tubules. Co-administration of MSG and α-tocopherol (200 mg/kg) significantly reduced the oxidative damage compared with MSG-treated group and also restored the normal renal function.Discussion: The results indicated that oxidative stress was involved in MSG-induced functional and pathological changes in the kidney. α-tocopherol modulates the functional disorder and maintains the normal architecture of renal tissue by reducing oxidative stress.Conclusion: The α-tocopherol may be a potent protective agent in combating MSG-induced renal toxicity.

Protective effect of α-Tocopherol on memory deficits and Na+,K+-ATPase and acetylcholinesterase activities in rats with diet-induced hypercholesterolemia

BackgroundWe investigate behavioral tests, acetylcholinesterase (AChE) and Na+,K+-ATPase activities in rats with diet-induced hypercholesterolemia feeding and α-tocopherol administration. MethodsWe tested a protocol with four groups: standard diet (control); high-fat diet (HF); α-tocopherol (α-Toc); HF plus α-tocopherol (HF+α-Toc). HF was administered ad libitum and α-Toc (50mg/kg) by gavage. After three months of treatment we performed the behavioral tests. The biochemical assays were performed ex vivo in the cerebral cortex (CC), hippocampus (HP) and blood samples. ResultsThe behavioral tests results showed a decrease in step-down latency for the HF group (P<0.05). When rats that received HF were treated with α-toc (HF+α-Toc) the step-down latency was similar to the control group. AChE and Na+,K+-ATPase activities in homogenate and synaptosomes was observed a significant decrease in CC and HP in HF group (P<0.05). However, α-Toc group showed to reverse the decline in AChE and Na+,K+-ATPase activities in CC and HP. HF group showed a significant increase (P<0.05) in MDA levels in CC and HP in relation to other groups. However, α-Toc group showed a significant decrease (P<0.05) in MDA levels when only compared with the HF group. Blood AChE activity increased in α-Toc group (P<0.05) and decreased in HF group (P<0.05) compared to all groups. ConclusionsThe present outcomes showed that treatment with α-Toc prevents the inhibition of AChE and Na+,K+-ATPase activities and consequently memory impairment induced by HF diet, demonstrating that this compound can modulate cholinergic neurotransmission and consequently improve cognition in this experimental condition.

Dependence of protective effect of α-tocopherol on its concentration and time of action on pc12 cells under conditions of oxidative stress

At the short-term incubation (0.5 and 1.5 h) of cells of the PC12 neuronal line with alpha-tocopherol, its protective effect against the cytotoxic hydrogen peroxide action was increased with rise of its concentration in samples; the protection was practically absent at action of nanomolar antioxidant concentrations, but was well expressed at its micromolar concentrations. These data agree with the concept that alpha-tocopherol increases the cell living activity by reacting directly with free radicals, which leads to formation of the less reactive compounds deprived of non-paired electron. The evidence is obtained that at the long-term action on PC12 cells, alpha-tocopherol not only in micro-, but also in nanomolar concentrations increases statistically significantly the cell living activity under conditions of oxidative stress. As follows from the obtained data, an important role in realization of the alpha-tocopherol protective effect at the long-term incubation with it seems to be played by modulation by this antioxidant of activity of protein kinase activated by extracellular signaling, phosphatidylinosite 3-kinase, and protein kinase C.

Alpha-tocopherol at nanomolar concentrations increases the viability of PC12 cells under oxidative stress conditions. The effects of modulation of signaling systems

We found that long-term preincubation of neuronal-like PC12 cells with α-tocopherol at micro- as well as nanomolar concentrations significantly increased cell viability under oxidative stress conditions. We discovered that the protective effect of α-tocopherol increases with an increase in its concentration in the 1–100 nM range, while its effects at concentrations of 100 nM, 1, 10, and 100 μM were similar when α-tocopherol was applied to cells 12–18 h prior to H2O2. An important role in the protective effect of long-term pre-incubation of cells with α-tocopherol at various concentrations is probably related to its modulatory influence on the activities of protein kinase C, extracellular signal-activated protein kinase, and phosphatidylinositol 3-kinase. Short-term preincubation of PC12 cells with this antioxidant at nanomolar concentrations for 0.5 or 1.5 h practically did not influence cell viability, while the protective effect of α-tocopherol at micromolar concentrations was probably related to its ability to terminate free-radical reactions due to direct interactions with free radicals.

Protective effect of α-tocopherol on damage to rat testes by experimental cryptorchidism

It is thought that the degeneration of germ cells associated with an increase in the temperature due to cryptorchidism involves oxidative stress. α-Tocopherol is a powerful antioxidant that prevents oxidation of polyunsaturated fats found in membranes and stabilizes peroxyl radicals. For this reason we were interested in determining the role of α-Tocopherol using experimental cryptorchidism, followed by orchidopexia in neonatal rats. Eighty-four, 10-day-postpartum (dpp) male rats (Wistar strain) were used and divided into 7 groups: healthy control, sham with α-Tocopherol treated with 30 or 100 mg/kg doses, sham vehicle, cryptorchidism treated with α-Tocopherol at 30 or 100 mg/kg doses and cryptorchidism vehicle. Cryptorchidism was surgically induced at 10 dpp. At 25 dpp the animals were treated with α-Tocopherol and the vitamin vehicle. Lipoperoxidation and testicular morphology was determined in half of the animals at 40 dpp (short term). The remaining animals underwent orchidopexia and fertility was determined at 90 dpp. Testicular morphology was determined at 120 dpp (long term) in these animals. A significant reduction of lipoperoxidation was observed in the cryptorchid group treated with α-Tocopherol compared to the untreated cryptorchid group, in addition to short-term histological alterations. At long term, we observed an increase in the area and maturation of the seminiferous epithelium, a decrease in apoptosis and histological alterations and an increase in fertility from α-Tocopherol treatment. α-Tocopherol treatment decreased lipoperoxidation, possibly stabilizing free radicals produced during cryptorchidism, reducing morphological testicular alterations and favoring fertility.

Protective Effects of α-Tocopherol on ABR Threshold Shift in Rabbits Exposed to Noise and Carbon Monoxide.

Noise induced hearin gloss (NIHL) is one of the most important occupational disease world wide. NIHL has been found potentiate by simultaneous carbon monoxide (CO) exposure. Free radicals have been implicated in cochlear damage resulted from the exposure to noise and due to the CO hypoxia. This study examined whether α-tocopherol administration , as a free radical scavenger, causes the attenuation of auditory brainstem response (ABR) threshold shifts resulting from noise exposure and noise plus CO exposure. Forty-two rabbits were divided in to seven groups including control, noise + saline, noise + CO + saline, noise + α-tocopherol, noise + CO + α-tocopherol , CO + α-tocopherol and α-tocopherol alone. ABR was assessed before exposure, 1 hand 14 days post exposure. The administration of 50 mg/Kg of α-tocopherol prior, following and post exposure to noise or noise plus CO recovered permanent ABR threshold shift at 1 and KHz almost to the baseline and provided significant attenuation in permanent ABR threshold shift at 4 and 8 KHz in subject swhich were exposed to noise but it did not block the potentiating of threshold elevation by CO exposure (extra threshold loss by combined exposure) at 4 and 8 KHz. α Tocopherol provides protective effect against the hearing loss resulting from noise exposure and simultaneous exposure to noise plus CO.