Association between alcohol-induced oxidative stress and membrane properties in synaptosomes: A protective role of vitamin E.

Reddy VD, Padmavathi P, Bulle S, Hebbani AV, Marthadu SB, Venugopalacharyulu NC, Maturu P, Varadacharyulu NC

Neurotoxicol Teratol. 2017 Sep;63:60-65. doi: 10.1016/j.ntt.2017.07.004. Epub 2017 Aug 1.

Abstract

Chronic and excessive alcohol consumption leads to various neurological diseases. Synaptosomes are ideal organelles to study the functional properties of the brain in alcoholism. This study focuses on the association between oxidative stress and synaptosomal membrane properties in alcohol treated rats. Sixty day old male albino rats were treated with 20% alcohol at 5g/kg body weight/ day for sixty days. Alcohol administration significantly increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls with decreased catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and reduced glutathione (GSH) content in synaptosomes. Further, alcohol administration decreased (cholesterol/phospholipids) C/P ratio in synaptosomal membranes, which was further confirmed using 1,6 diphenyl 1,3 hexatriene (DPH) as fluorescent probe. Moreover, alcohol treatment also increased membrane bound Na⁺/K⁺-ATPase, Ca²⁺-ATPase and Mg²⁺-ATPase enzyme activities. Correlation (r) analysis revealed that anisotropic (γ) values were strongly associated with lipid peroxidation (r=0.678) and Na⁺/K⁺-ATPase activity (r=0.793). The results of the present study clearly indicate that lipid peroxidation was positively correlated (r=0.621) with Na⁺/K⁺-ATPase activity and C/P ratio was negatively associated (r=-0.549) in alcohol treated animals. Similar results were found on alcohol treatment (50 and 100mM) of brain synaptosomes in vitro. But with the co-treatment of vitamin E reversed these changes. In conclusion, synaptosomal membranes properties are impaired due to increased oxidative stress, changes in lipid composition, altered fluidity and membrane bound enzyme activities. And treatment with vitamin E renders protection against ethanol-induced membrane alterations.

Zhang J, Song W, Sun Y, Shan A

Environ Sci Pollut Res Int. 2017 Sep 16. doi: 10.1007/s11356-017-0104-1. [Epub ahead of print]

Abstract

Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg^-1 (per body weight) of phoxim, 200 mg kg^-1 (per body weight) of vitamin E, and phoxim + vitamin E. The results showed that exposure to phoxim elevated liver coefficient; glutamyl transpeptidase (GGT), aspartate aminotransferase, alkaline phosphatase, total bilirubin, total bile acid, and alanine aminotransferase in the serum; ROS in the liver; and the expression of p53, Bax, CYP2E1, ROS, caspase-9, caspase-8, and caspase-3, while phoxim caused a reduction of total protein, albumin, and cholinesterase in the serum; acetylcholinesterase, total antioxidant capacity, glutathione peroxidase, and glutathione in the liver; and the expression of Bcl-2. Vitamin Emodified the phoxim-induced hepatotoxicity by reducing the GGT in the serum, malondialdehyde in the liver, and the expression of CYP2E1 significantly. There were no significant changes of globulin in the serum, the activity of catalase in the liver, as well as expression levels of Fas and Bad in the liver. Overall, subacute exposure to phoxim induced hepatic injury, oxidative stress damage, and cell apoptosis. Vitamin Emodified phoxim-induced hepatotoxicity slightly. And, vitamin E minimized oxidative stress damage and ultrastructural changes in rat hepatocytes notably.

Duan L, Li J, Ma P, Yang X, Xu S

Food Chem Toxicol. 2017 Sep;107(Pt A):47-56. doi: 10.1016/j.fct.2017.06.025. Epub 2017 Jun 15.

Abstract

Millions of people are regularly exposed to ozone, a gas known to contribute significantly to worsening the symptoms of patients with asthma. However, the mechanisms underlying these ozone exacerbation effects are not fully understood. In this study, we examined the exacerbation effect of ozone in OVA-induced asthma mice and tried to demonstrate the protective mechanism of vitamin E (VE). An asthma mouse model was established, and used to identify the exacerbating effects of ozone by assessing cytokine and serum immunoglobulin concentrations, airway leukocyte infiltration, histopathological changes in lung tissues, and airway hyper-responsiveness. We then determined the amount of reactive oxygen species (ROS) accumulated, the extent to which VE induced ROS elimination, and examined the antagonistic effects of VE on the ozone-induced exacerbating effects. This study showed that 1-ppm ozone exposure could exacerbate OVA-induced asthma in mice. More importantly we found that ozone induced oxidative stress in asthmatic airways may lead to the inhibition of Nuclear factor-erythroid 2-related factor 2 (Nrf2), and may subsequently induce even more exaggerated oxidative stress associated with asthma exacerbation. Through VE induced Nrf2 activation and the subsequent increase in Nrf2 target protein expression, this study suggests a novel mechanism for alleviating ozone exacerbated asthma symptoms.

Bivona JJ, Patel S, Vajdy M

Expert Opin Biol Ther. 2017 Sep 14:1-13. doi: 10.1080/14712598.2017.1375096. [Epub ahead of print]

Abstract

INTRODUCTION:

Vitamins E and C are well known small molecules that have been used to maintain health for decades. Recent studies of the cellular and molecular pathways leading to immunomodulation by these molecules have been of interest, as have their anti-oxidant properties and signal transduction pathways for curing or improving infectious diseases and cancer. Areas covered: Herein, the authors provide a definition and the structural classification of vitamins E and C and how these molecules influence cellular function. The studies include in vitro, ex vivo and in vivo studies in animal models as well as clinical trials. The authors give particular focus to the scientifically factual and putative roles of these molecules in innate and adaptive immunomodulation and prevention or cure of diseases. Expert opinion: The antioxidant properties of vitamins E and C are well studied. However, whether there is a link between their antioxidant and immunomodulation properties is unclear. In addition, there is a strong, albeit putative, prevailing notion that vitamin C can prevent or cure infectious diseases or cancer. Presently, while there is proven evidence that vitamin E possesses immunomodulatory properties that may play a positive role in disease outcomes, this evidence is less available for vitamin C.

Peh HY, Tan WSD, Chan TK, Pow CW, Foster PS, Wong WSF.

Free Radic Biol Med. 2017 Sep;110:332-344. doi: 10.1016/j.freeradbiomed.2017.06.023. Epub 2017 Jul 3.

Abstract

Inflammation and oxidative stress contribute to emphysema in COPD. Although corticosteroids are the standard of care for COPD, they do not reduce oxidative stress, and a subset of patients is steroid-resistant. Vitamin E isoform γ-tocotrienol possesses both anti-inflammatory and anti-oxidative properties that may protect against emphysema. We aimed to establish the therapeutic potential of γ-tocotrienol in cigarette smoke-induced COPD models in comparison with prednisolone. BALB/c mice were exposed to cigarette smoke for 2 weeks or 2 months. γ-Tocotrienol and prednisolone were given orally. Bronchoalveolar lavage (BAL) fluid and lung tissues were assessed for inflammation, oxidative damage, and regulation of transcription factor activities. Emphysema and lung function were also evaluated. γ-Tocotrienol dose-dependently reduced cigarette smoke-induced BAL fluid neutrophil counts and levels of cytokines, chemokines and oxidative damage biomarkers, and pulmonary pro-inflammatory and pro-oxidant gene expression, but restored lung endogenous antioxidant activities. γ-Tocotrienol acted by inhibiting nuclear translocation of STAT3 and NF-κB, and up-regulating Nrf2 activation in the lungs. In mice exposed to 2-month cigarette smoke, γ-tocotrienol ameliorated bronchial epithelium thickening and destruction of alveolar sacs in lungs, and improved lung functions. In comparison with prednisolone, γ-tocotrienol demonstrated better anti-oxidative efficacy, and protection against emphysema and lung function in COPD. We revealed for the first time the anti-inflammatory and antioxidant efficacies of γ-tocotrienol in cigarette smoke-induced COPD models. In addition, γ-tocotrienol was able to attenuate emphysematous lesions and improve lung function in COPD. γ-Tocotrienol may have therapeutic potential for the treatment of COPD.

Kalantari A, Saremi A, Shavandi N, Foroutan Nia A

Urol J. 2017 Aug 29;14(5):5023-5026.

Abstract

PURPOSE:

The aim of this study was to evaluate the effect of 4 week intensive swimming exercise and alpha-tocopherol supplementation on testicular oxidative stress and spermatogenesis in rats.

MATERIALS AND METHODS:

40 male rats were randomly assigned to Control (C), Sham (S), Exercise (E) and Exercise + supplement (ES) groups. Exercise training performed for 4 weeks (1session/day, 6days/week). Each session included 180 minutes of swimming. In ES group, alpha-ocopherol was injected at a dose of 50 mg/kg/day. 48 hours after last training session, all rats were killed and gonads of them were removed from their body for histological and biochemical assays. All statistical analysis was performed by SPSS 16. P values less than 0.05 were considered as statistically significant.

RESULTS:

Total testicular antioxidant capacity increased significantly in E (P = .003) and ES groups (P = .001) whereas there was no significant difference between C and E group in testicle Malondialdehyde (a lipid peroxidation marker) level (P = .999) and spermatogenesis quality (P = .381). Testicle Malondialdehyde level decreased (P = .009) and spermatogenesis quality was improved significantly in ES group (P = .001).

CONCLUSION:

Alpha-tocopherol supplementation is effective in order to improve spermatogenesis process in athletes who exercise with high intensity.

Nur Azlina MF, Qodriyah HMS, Chua KH, Kamisah Y

World J Gastroenterol. 2017 Aug 28;23(32):5887-5894. doi: 10.3748/wjg.v23.i32.5887.

Abstract

AIM:

To investigate and compare the effects of tocotrienol and omeprazole on gastric growth factors in rats exposed to water-immersion restraint stress (WIRS).

METHODS:

Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF-α) mRNA expression.

RESULTS:

Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control (S) group was increased (P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF (P < 0.001), bFGF (P < 0.001) and TGF-α (P < 0.001) mRNA levels and caused an increase in EGF mRNA (P < 0.001) that was statistically significant compared to the non-stressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF (P = 0.008), bFGF (P = 0.001) and TGF-α (P = 0.002) mRNA.

CONCLUSION:

Tocotrienol provides gastroprotective effects in WIRS-induced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.

Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP

Drug Discov Today. 2017 Aug 5. pii: S1359-6446(17)30137-X. doi: 10.1016/j.drudis.2017.08.001. [Epub ahead of print]

Abstract

Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials. This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases.

Rýdlová M, Růnová K, Száková J, Fučíková A, Hakenová A, Mlejnek P, Zídek V, Tremlová J, Mestek O, Kaňa A, Zídková J, Melčová M, Truhlářová K, Tlustoš P.

Biomed Res Int. 2017;2017:6759810. doi: 10.1155/2017/6759810. Epub 2017 May 30.

Abstract

The response of nutrient status and biochemical processes in (i) Wistar and (ii) spontaneously hypertensive (SHR) rats upon dietary intake of selenium- (Se-) enriched defatted rapeseed (DRS) and/or vitamin E fortification was examined to assess the health benefit of DRS in animal nutrition. Twenty-four individuals of each type of rat were used: The control group was fed with an untreated diet (Diet A). In Diets B and C, soybean meal was replaced with defatted DRS, which comprised 14% of the total diet. The selenized DRS application resulted in ~3-fold increase of Se content in the diet. Diet C was also fortified with the addition of vitamin E, increasing the natural content by 30%. The Se content of the blood and kidneys tended to increase in the DRS groups, where the changes were significant (P < 0.05) only in the case of SHR rats. The iodine (I) content and the proportion of iodide in rat livers indicated a lower transformation rate of iodide into organoiodine compounds compared to the control. Slight and ambiguous alterations in the antioxidative response of the rat were observed in the DRS groups, but the addition of vitamin E to the diet helped to moderate these effects.

Libinaki R, Vinh A, Tesanovic-Klajic S, Widdop RE, Gaspari TA.

Clin Exp Pharmacol Physiol. 2017 Jul 26. doi: 10.1111/1440-1681.12821. [Epub ahead of print]

Abstract

α-Tocopheryl phosphate (TP) is a naturally occurring form of Vitamin E found in the body. In the present study we compared the ability of an α-TP mixture (TPM) against a standard Vitamin E supplement, α-tocopherol acetate (TA) on the development of atherosclerotic lesions in ApoE-deficient mice. Mice were maintained on either a normal chow diet for 24 weeks (Normal Diet), versus a group in which the final 8 weeks of the 24 week period mice were placed on a high fat (21%), high cholesterol (0.15%) challenge diet (HFHC), to exacerbate atherosclerotic lesion development.. The difference in these two control groups established the extent of the diet induced atherosclerotic lesion development. Mice in the various treatment groups received either TA (300mg/kg chow) or TPM (6.7 to 200mg/kg chow) for 24 weeks, with TPM treatment resulting in dose-dependent significant reductions in atherosclerotic lesion formation and plasma levels of pro-inflammatory cytokines. TA-treated mice, with the tocopherol equivalent TPM dose (200mg/kg chow), showed no significant reduction in plasma lipid levels or evidence for aortic lesion regression. At this TPM equivalent TA dose, a 44% reduction in aortic lesion formation was observed. In addition, these TPM treated mice, also showed a marked reduction in aortic superoxide formation and decreased circulating plasma levels of known pro-inflammatory markers IL-6, MCP-1, IL-1β, IFN-γ and TNF-α. These findings indicate that TPM treatment slows progression of atherosclerotic lesions in ApoE-deficient mice with this effect potentially involving reduced oxidative stress and decreased inflammation.