Vitamin E antagonizes ozone-induced asthma exacerbation in Balb/c mice through the Nrf2 pathway.

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

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

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.

Remely M, Ferk F, Sterneder S, Setayesh T, Kepcija T, Roth S, Noorizadeh R, Greunz M, Rebhan I, Wagner KH, Knasmüller S, Haslberger A.

Nutrients. 2017 Jun 14;9(6). pii: E607. doi: 10.3390/nu9060607.

Abstract

Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1. Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity-and oxidative stress-induced health risks.

Tucker LA.

Nutrients. 2017 Jun 13;9(6). pii: E601. doi: 10.3390/nu9060601.

Abstract

Antioxidants have a number of potential health benefits. The present investigation was designed to determine the relationship between serum alpha- and gamma-tocopherol levels (powerful antioxidants), and leukocyte telomere length (a biomarker of biological aging). A cross-sectional design was employed to study 5768 adults from the National Health and Nutrition Examination Survey (NHANES). DNA was obtained via blood samples. Telomere length was assessed using the quantitative polymerase chain reaction method. Serum concentrations of alpha- and gamma-tocopherol were measured using high performance liquid chromatography (HPLC). Results showed that for each one-year increase in age, telomeres were 15.6 base pairs shorter (F = 410.4, p < 0.0001). After adjusting for differences in the demographic covariates, for each µg/dL higher level of gamma-tocopherol, telomeres were 0.33 base pairs shorter (F = 7.1, p = 0.0126). Telomeres were approximately 1 year shorter (15.6 base pairs) for each increment of 47.3 to 55.7 µg/dL of gamma-tocopherol in the blood, depending on the variables controlled. Adults at the 75th percentile of gamma-tocopherol had 2.8-3.4 years greater cellular aging than those at the 25th percentile, depending on the covariates in the model. However, alpha-tocopherol was not related to telomere length. Evidently, gamma-tocopherol levels, but not alpha-tocopherol, account for meaningful increases in biological aging.

Halvaei Z, Tehrani H, Soltaninejad K, Abdollahi M, Shadnia S.

Turk J Med Sci. 2017 Jun 12;47(3):795-800. doi: 10.3906/sag-1512-6.

Abstract

BACKGROUND/AIM:

Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specific antidote for its treatment, the aim of this study was to evaluate the effect of vitamin E in the treatment of acute AlP poisoning.

MATERIALS AND METHODS:

This was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition, the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma were measured.

RESULTS:

There was no significant difference between the treatment and control groups with regard to demographic, clinical, or paraclinical data or Simplified Acute Physiology Score II (SAPS_II) on admission. Systolic blood pressure significantly increased during the first 24 h in the treatment group (P < 0.05). The plasma MDA level significantly decreased in the treatment group (P < 0.05). Vitamin E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It significantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05).

CONCLUSION:

Vitamin E along with supportive treatment could have a therapeutic effect in acute AlP poisoning.

Cansev M, Turkyilmaz M, Sijben JWC, Sevinc C, Broersen LM, van Wijk N.

J Alzheimers Dis. 2017 Jun 9. doi: 10.3233/JAD-170081. [Epub ahead of print]

Abstract

Chronic consumption of a diet enriched with nutritional precursors of phospholipids, including uridine and the polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), was shown previously to enhance levels of brain phospholipids and synaptic proteins in rodents. Vitamin C, vitamin E, and selenium may directly affect the breakdown or synthesis of membrane phospholipids. The present study investigated the necessity of antioxidants for the effectiveness of supplementation with uridine plus DHA and EPA (as fish oil) in rats. Rats were randomized to four treatment groups and received, for 6 weeks, one of four experimental diets, i.e., a diet low in antioxidants, a diet high in antioxidants, a diet low in antioxidants supplemented with DHA+EPA+uridine, or a diet high in antioxidants supplemented with DHA+EPA+uridine. On completion of dietary treatment, rats were sacrificed, and brain levels of phospholipids, synaptic proteins, and two enzymes involved in phospholipid synthesis (choline-phosphate cytidylyltransferase, PCYT1A, and choline/ethanolamine phosphotransferase, CEPT1) were analyzed. Levels of phospholipids, the pre- and post-synaptic proteins Synapsin-1 and PSD95, and the enzymes PCYT1A and CEPT1 were significantly enhanced by combined supplementation of DHA+EPA+uridine and antioxidants and not enhanced by supplementation of DHA+EPA+uridine with insufficient antioxidant levels. Our data suggest that dietary vitamin C, vitamin E, and selenium are essential for the phospholipid precursors’ effects on increasing levels of membrane phospholipids and synaptic proteins, the indirect indicators of synaptogenesis. Their concomitant supply may be relevant in Alzheimer’s disease patients, because the disease is characterized by synapse loss and lower plasma and brain levels of phospholipid precursors and antioxidants.

Horák D, Pustovyy VI, Babinskyi AV, Palyvoda OM, Chekhun VF, Todor IN, Kuzmenko OI.

Int J Nanomedicine. 2017 Jun 6;12:4257-4268. doi: 10.2147/IJN.S137574. eCollection 2017.

Abstract

Maghemite (γ-Fe₂O₃) nanoparticles were obtained by coprecipitation of ferrous and ferric salts in an alkaline medium followed by oxidation; the nanoparticles were coated with poly(N,N-dimethylacrylamide) (PDMA) and characterized by transmission electron microscopy, attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering, thermogravimetric and elemental analyses, and magnetic measurements in terms of particle morphology, size, polydispersity, amount of coating, and magnetization, respectively. The effects of α-tocopherol (Toc) and its phenolic (Toc-6-OH) and acetate (Toc-6-Ac) derivatives on Fe²⁺ release from γ-Fe₂O₃@PDMA, as well as from γ-Fe₂O₃ and CuFe₂O₄ nanoparticles (controls), were examined in vitro using 1,10-phenanthroline. The presence of tocopherols enhanced spontaneous Fe²⁺ release from nanoparticles, with Toc-6-OH exhibiting more activity than neat Toc. All of the nanoparticles tested were found to initiate blood lipid oxidation in a concentration-dependent manner, as determined by analysis of 2-thiobarbituric acid reactive species. Wistar rats with Walker-256 carcinosarcoma (a model of mammary gland carcinosarcoma) received Toc-6-Ac, magnetic nanoparticles, or their combination per os, and the antitumor activity of each treatment was determined in vivo. γ-Fe₂O₃@PDMA nanoparticles exhibited increased antitumor activity compared to both commercial CuFe₂O₄ particles and the antitumor drug doxorubicin. Moreover, increased antitumor activity was observed after combined administration of γ-Fe₂O₃@PDMA nanoparticles and Toc-6-Ac; however, levels of bilirubin, aspartate aminotransferase, and white bloods normalized and did not differ from those of the intact controls. The antitumor activity of the γ-Fe₂O₃ nanoparticles strongly correlated with Fe²⁺ release from the nanoparticles but not with nanoparticle-initiated lipid peroxidation in vitro.

Hochberg I, Berinstein EM, Milman U, Shapira C, Levy AP

Curr Diab Rep. 2017 Jun;17(6):42. doi: 10.1007/s11892-017-0868-1.

Abstract

PURPOSE OF REVIEW:

Despite compelling evidence regarding the importance of oxidant stress in the development of vascular complications and observational studies suggesting that vitamin E may be protective from these complications, multiple clinical trials have failed to show benefit from vitamin E supplementation in the prevention of vascular complications in diabetes. One possible explanation for this failure of vitamin E may have been inappropriate patient selection. This review seeks to provide the clinical evidence and mechanistic basis for why a subset of individuals defined by their haptoglobin (Hp) genotype may derive cardiovascular protection by vitamin E supplementation.

RECENT FINDINGS:

Clinical trial data from the HOPE, ICARE, and WHS studies is presented showing a pharmacogenomic interaction between the Hp genotype and vitamin E on the development of CVD. Specifically, in individuals with diabetes and the Hp2-2 genotype, vitamin E has been shown to be associated with an approximately 35% reduction in CVD. Cardioprotection by vitamin E in individuals with the Hp2-2 genotype appears to be mediated in part by an improvement in HDL functionality as demonstrated in three independent trials in both type 1 diabetes and type 2 diabetes. Vitamin E may provide benefit in reducing CVD in Hp2-2 individuals with diabetes. However, in order for this pharmacogenomic algorithm to be accepted as a standard of care and used clinically, an additional large prospective study will need to be performed.

El-Faras AA, Sadek IA, Ali YE, Khalil M, Mussa EB.

Physiol Int. 2016 Jun 1;103(2):157-168. doi: 10.1556/036.103.2016.2.3.

Abstract

The increased generation of free radicals plays an important role in testicular damage. The present study aimed to investigate the adverse effects of carbon tetrachloride (CCl₄) on the reproductive system of male rats as well as to examine whether Vitamin E (VE) is able to ameliorate these effects. The rats were equally divided into three groups: control, CCl₄-treated, and CCl₄ + VE-treated groups. After 4 weeks of treatment, the decrease in body and testes weights, sperm parameters, and the decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone of CCl₄-treated rats were ameliorated by VE treatment. The co-administration of VE with CCl₄significantly decreased the level of lipid peroxidation production (malondialdehyde) and increased the activity of anti-oxidant enzymes (superoxide dismutase and catalase) when compared with the CCl₄ group. Moreover, VE prevented CCl₄-induced severe testicular histopathological lesions and deformities in spermatogenesis. The results demonstrate that VE augments the anti-oxidants’ defense mechanism against CCl₄-induced reproductive toxicity suggesting a therapeutic role in free radical-mediated infertility.

Tang HY, Ho HY, Chiu DT, Huang CY, Cheng ML, Chen CM

Clin Chim Acta. 2017 May 2;470:75-80. doi: 10.1016/j.cca.2017.05.001. [Epub ahead of print]

Abstract

BACKGROUND:

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy resulting in demyelination in peripheral nervous system. Myelin enriched in lipids is easily oxidized by reactive oxygen species during inflammation. Oxidative stress and lipophilic anti-oxidative capacities in GBS patients have not been fully explored. To evaluate the redox status of GBS patients, we measured malondialdehyde (MDA), myeloperoxidase (MPO), lipophilic antioxidants, and tocopherols concentrations in plasma from GBS patients and age-matched healthy controls.

RESULTS:

Concentrations of γ-tocopherol and δ-tocopherol decreased significantly, and α-carotene significantly increased in GBS patients compared to healthy controls. However, no significant changes in MDA and MPO concentrations were detected. In GBS patients, the γ-tocopherol concentration correlated positively with concentrations of δ-tocopherol, α-tocopherol, lutein, Q10, and γ-CEHC, respectively. Similarly, the δ-tocopherol concentration correlated positively with γ-tocopherol, α-tocopherol, lutein, Q10, δ-CEHC, and γ-CEHC concentrations, respectively. The receiver operating characteristics curve analysis showed that γ-tocopherol may serve as a good predictor for GBS.

CONCLUSIONS:

Diminished lipophilic antioxidant defense, mainly γ-tocopherol and δ-tocopherol, in GBS patients accounting for their lowered resistance to reactive oxygen species is probably associated with pathogenesis of GBS, and potentially useful for the development of therapeutic strategies.

Jia YB, Jiang DM, Ren YZ, Liang ZH, Zhao ZQ, Wang YX.

Mol Med Rep. 2017 Apr;15(4):1585-1592. doi: 10.3892/mmr.2017.6160. Epub 2017 Feb 2.

Abstract

Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid‑induced femoral head necrosis. Vitamin E demonstrates anti‑apoptotic and anti‑oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid‑induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E‑treated, and control groups), each comprising 12 rabbits. Those in the steroid group (group S) were initially injected twice with an intravenous dose of 100 µg/kg Escherichia coli endotoxin, with a 24 h interval between the two injections, and then with an intramuscular dose of 20 mg/kg methylprednisolone, three times at intervals of 24 h in order to establish a rabbit model of osteonecrosis. The vitamin E treated group (group E) received the same treatment as group S, and were administered 0.6 g/kg/d vitamin E daily from the beginning of modeling. The control group (group C) was injected with normal saline at the equivalent dosage and times as the aforementioned two groups. Two time points, weeks 4 and 6 following the completion of modeling, were selected. Osteonecrosis was verified by histopathology with hematoxylin-eosin staining. The apoptosis rate of osteonecrosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The apoptosis expression levels of caspase‑3 and B‑cell lymphoma 2 (Bcl‑2), and DNA oxidative damage of bone marrow hematopoietic cells were analyzed by immunohistochemistry. At weeks 4 and 6 following the completion of modeling, the vacant bone lacunae rates of group E were 15.87±1.97 and 25.09±2.67%, respectively, lower than the results of 20.02±2.21 and 27.79±1.39% for group S; and the osteocyte apoptosis indexes of group E were 20.99±2.95 and 33.93±1.62%, respectively, lower than the results of 26.46±3.37 and 39.90±3.74% from group S. In addition, the Bcl-2 expression at week 4 in the femoral head tissues of group E was higher compared with group S; and the proportion of Bcl‑2‑positive cells of group E was 9.81±1.01%, higher compared with group S at 8.26±1.13%. The caspase‑3 staining data at week 4 in femoral head tissues demonstrated that in the 12 femoral heads of group S, four were negative (32%) and eight were positive (68%); in group E, five were negative (45%) and seven were positive (55%); and in group C, 11 were negative (95%) and one was positive (5%). In addition, the DNA oxidative damage rate at week 4 in the bone marrow hemopoietic cells of group E was (7.24±1.44%), lower compared with group S (11.80±1.26%), and higher compared with group C (5.75±1.47%). Vitamin E is effective in intervening in apoptosis through decreasing caspase‑3 expression and upregulating Bcl‑2 expression, and by alleviating DNA oxidative damage in bone marrow hemopoietic cells at the early stage of steroid‑induced femoral head necrosis in rabbit models.