Extracellular stimuli signal for activation of the transcription factor NFkappaB, leading to gene expression regulating processes involved in immune responses, inflammation, and cell survival. Tumor necrosis factor-alpha (TNFalpha) activates NFkappaB via a well-defined kinase pathways involving NFkappaB-inducing kinase (NIK), which activates downstream multisubunit IkappaB kinases (IKK). IKK in turn phosphorylates IkappaB, the central regulator of NFkappaB function. We found that intracellular vitamin C inhibits TNFalpha-induced activation of NFkappaB in human cell lines (HeLa, monocytic U937, myeloid leukemia HL-60, and breast MCF7) and primary endothelial cells (HUVEC) in a dose-dependent manner. Vitamin C is an important antioxidant, and most cells accumulate ascorbic acid (AA) intracellularly by transporting the oxidized form of the vitamin, dehydroascorbic acid (DHA). Because ascorbic acid is a strong pro-oxidant in the presence of transition metals in vitro, we loaded cells with vitamin C by incubating them with DHA. Vitamin C-loaded cells showed significantly decreased TNFalpha-induced nuclear translocation of NFkappaB, NFkappaB-dependent reporter transcription, and IkappaBalpha phosphorylation. Our data point to a mechanism of vitamin C suppression of NFkappaB activation by inhibiting TNFalpha-induced activation of NIK and IKKbeta kinases independent of p38 MAP kinase. These results suggest that intracellular vitamin C can influence inflammatory, neoplastic, and apoptotic processes via inhibition of NFkappaB activation.

Modulating mitochondrial antioxidant status is a nutritional issue of great interest in the treatment or prevention of several oxidative stress related diseases such as obesity. Thus, the aim of the present study was to analyze the effects of three antioxidants on hepatic mitochondrial function and antioxidant status. Isolated rat liver mitochondria were incubated with vitamin C, resveratrol and lipoic acid. The activity of antioxidant enzymes (manganese superoxide dismutase and glutathione peroxidase), ROS generation and respiratory parameters (RCR, P/O ratio and respiratory states) were measured. Vitamin C influenced mitochondrial function by decreasing of ROS generation (P<0.0001), by stimulating the activity of manganese superoxide dismutase (197.60± 35.99%; P<0.001) as well as glutathione peroxidase (15.70± 5.76%; P<0.05) and by altering the activity of the electron transport chain, mainly by decreasing the P/O ratio (P<0.05). Resveratrol induced a significant increase in manganese superoxide dismutase activity (160± 11.78%; P<0.0001) and a decrease in ROS generation (P<0.05 to P<0.0001). By contrast, lipoic acid inhibited glutathione peroxidase activity (16.48± 3.27%; P<0.05) and induced the uncoupling of the electron transport chain (P<0.01). Moreover, this antioxidant induced a strong decrease in the P/O ratio (P<0.05 to P<0.0001). In conclusion, our results suggest that the three tested antioxidants produced direct effects on mitochondrial function, although the magnitude and intensity of these actions were significantly different, which may have implications when administrated as antioxidants.

The purpose of this study was to determine whether vitamin E or vitamin C supplementation alters the DNA damage of whole blood white blood cells (WBC) in patients with chronic obstructive pulmonary disease (COPD). Thirty-five patients with stable COPD were recruited in this randomized and placebo-controlled study. Patients were randomly assigned to placebo (n = 8), 400 mg/day vitamin E (E400, n = 9), 200 mg/day vitamin E (E200, n = 9), or 250 mg/day vitamin C (C250, n = 9) for 12 weeks. The results showed that vitamin E or C supplementation did not significantly change the mean level of endogenous DNA breakages. Whereas, after 12 weeks of vitamin supplementation, the H2O2-induced DNA breakages were significantly suppressed by 45%, 59%, and 52%, respectively, in E400, E250 and C250 groups (p < 0.05). In addition, neither the level of thiobarbituric acid-reactive substances (TBARS) nor spirometric parameters were significantly changed after 12 weeks of supplementation. In conclusion, vitamin E or C supplementation for 12 weeks may improve the resistance of DNA in whole blood WBC against oxidative challenge, although more research is needed to demonstrate the beneficial effect on slowing the decline of lung function in patients with COPD.

A new conception of the action mechanisms of vitamins and some other compounds without a vitamin status is briefly presented. It is based on results obtained through pulse radiolysis, molecular radiation biological investigations, and in vitro studies. The data clearly show that antioxidant vitamins (C, E, β-carotene) and B vitamins and related compounds possess the capability to emit"solvated electrons"in aqueous solutions or polar media. In consequence, the well-known vitamin effects are attributed to the action of the emitted solvated electrons and the resulting vitamin free radicals rather than the vitamin molecules per se, as generally accepted.

The present study evaluated the synergistic effects of the association of ascorbic acid andα-tocopherol on myenteric in the jejunum of diabetic rats. The rats were randomly divided into four equal groups: untreated normoglycemic (UC), untreated diabetic (UD), ascorbic acid and α-tocopherol-treated normoglycemic (CAE) and ascorbic acid and α-tocopherol-treated diabetic (DAE). The rats from the CAE and DAE group received supplementation with ascorbic acid (1g/L in water) and α-tocopherol (1% in chow). At 210-days-old, the animals were sacrified and their jejunum was collected and submitted to immunohistochemistry. Quantitative and/or morphometric analysis were performed. Supplementation with ascorbic acid and α-tocopherol prevented the cell loss of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We also observed a reduction of the CGRP nerve fiber varicosities and the prevention of the increased cell body size of submucosal VIP neurons (p<0.05). The association of ascorbic acid andα-tocopherol reduced the deleterious effects of diabetes promoting protection on the enteric neurons.

Curcumin (Cur) is a promising antioxidant and anticancer drug, but several recent studies indicate that Cur exerts its anticancer activity through promoting reactive oxygen species (ROS) generation. In the present study, concentration-dependent regulation of Cur on cell proliferation, viability and ROS generation, and effect of water-soluble antioxidants ascorbic acid (ASA), N-acetyl-cysteine (NAC) and reduced glutathione (GSH) on the antioxidant and anticancer activity of Cur were investigated in human myeloid leukemia cells (HL-60 cells). We found that although Cur concentration- and time-dependently decreased the proliferation and viability of cells, its effect on ROS generation (as indicated by the level of malondialdehyde, MDA) varied with its concentrations. I.e., low concentrations of Cur diminished the ROS generation, while high Cur promoted it. Combined with the opposite effect of 50 microM H2O2 on low or high Cur-induced MDA alteration, cell proliferation arrest and cell death, these results proved that low Cur exerted its anticancer activity through diminishing ROS generation in HL-60 cells, while high Cur through promoting ROS generation. Further studies showed that all water-soluble antioxidants ASA, NAC and GSH significantly enhanced both the antioxidant and the anticancer activity of low Cur. Considering that the extra accumulation of ROS is harmful to normal cells, the data presented here indicate that instead of using high doses, combining low doses of Cur with water-soluble antioxidants is a better strategy for us to improve the anticancer activity of Cur.

BACKGROUND:Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis.

METHODS:Women with (WEN, n = 83) and without endometriosis (WWE, n = 80) were interviewed using a Food Frequency Questionnaire to compare their antioxidant intake (of vitamins and minerals). Then, the WEN participated in the application of a control (n = 35) and high antioxidant diet (n = 37) for four months. The high antioxidant diet (HAD) guaranteed the intake of 150% of the suggested daily intake of vitamin A (1050 microg retinol equivalents), 660% of the recommended daily intake (RDI) of vitamin C (500 mg) and 133% of the RDI of vitamin E (20 mg). Oxidative stress and antioxidant markers (vitamins and antioxidant enzymatic activity) were determined in plasma every month.

RESULTS:Comparison of antioxidant intake between WWE and WEN showed a lower intake of vitamins A, C, E, zinc, and copper by WEN (p<0.05, Mann Whitney Rank test). The selenium intake was not statistically different between groups. During the study, the comparison of the 24-hour recalls between groups showed a higher intake of the three vitamins in the HAD group. An increase in the vitamin concentrations (serum retinol, alpha-tocopherol, leukocyte and plasma ascorbate) and antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase) as well as a decrease in oxidative stress markers (malondialdehyde and lipid hydroperoxides) were observed in the HAD group after two months of intervention. These phenomena were not observed in the control group.

CONCLUSION:WEN had a lower intake of antioxidants in comparison to WWE. Peripheral oxidative stress markers diminished, and antioxidant markers were enhanced, in WEN after the application of the HAD.

Background Many clinical trials have evaluated the oxidative stress reduction and enhancement of antioxidant status following yogic practices, but a review has not been reported earlier. Present study is designed to systematically review the effect of yogic practices on oxidative stress and antioxidant status. Content Using the MEDLINE, EMBASE SCOPEMED, and Indian database electronic searches were performed through August 2016 using the keywords yoga AND oxidative stress OR antioxidant which yielded 97 studies. Selections were made to include only experimental studies written in English, published in peer-reviewed journals and investigating the effects of regular yogic practices on oxidative stress and antioxidant status in these studies. Summary and outlook Search yielded a total of 97 trials, 11 met rigorous criteria for final systematic review. Healthy population showed overall enhancement of antioxidant status and reduced oxidative stress following yogic practices. Diabetic patients showed increased glutathione, vitamin C content and superoxide dismutase activity and decreased malondialdehyde content following yogic practices. Prediabetic and hypertensive patients showed reduced malondialdehyde content following yogic practices. Renal disease patients showed decreased protein oxidation, and increased superoxide dismutase activity following yogic practices. Regular yogic practices can improve antioxidants and reduce oxidative stress in healthy, diabetic, prediabetic, hypertensive and renal disease patients. Studies on other disease population have rarely been reported and studies are very few to conclude strongly.