Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils

BACKGROUND: Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils. MATERIALS AND METHODS: Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively. RESULTS: Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis. CONCLUSION: Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.     

Analysis of the variable effect of dietary vitamin E supplements on experimental atherosclerosis

Vitamin E inhibits processes thought to be important in the development of atherosclerosis but clinical trials to determine its effect on cardiovascular disease have given variable results, the majority being negative. The reasons for this are unclear. Animal trials can be better controlled and use more rigorous measures of lesion progression than human trials. The present study reviewed trials using rabbits and mice to determine whether they also are variable and, if so, to uncover methodological differences that may account for the different outcomes. A large number of trials examining the effect of vitamin E supplements on experimental atherosclerosis were identified. Using rigorous selection criteria, a well-defined group was selected for further investigation. Almost all the mice trials showed a significant effect of vitamin E, but only around one-third of the rabbit trials did so. When the rabbit trials were divided into those that did and those that did not observe significant effects, no single factor was found that could account for the dichotomy. However, when the percentage reduction in disease was considered, rather than the within-trial significance level, there were clear dose-dependent effects of vitamin E on disease severity in heritable hyperlipidaemic rabbits, and in genetically normal rabbits made hyperlipidaemic with cholesterol alone; the dose dependence was different in the two groups, the heritable hyperlipidaemic rabbits showing a near ten-fold lower sensitivity. The high doses required to affect experimental atherosclerosis may, if applicable to other species, help explain the absence of effects in many human trials.     

Views on antioxidant mouthwashes as adjunct in periodontal therapy

Clinical decision is often difficult with chlorhexidine mouthwash. The use of antioxidant mouthwashes for the treatment of periodontal disease is in practise. Therefore, it is of interest to collect gleaned information on Antioxidant mouthwashes as periodontal therapy from known literature. Improvement in treatment using antioxidant mouthwashes is reported in several studies. The mouthwash with antioxidants has similar anti-gingivitis, antiplaque and antimicrobial effects as that of chlorhexidine mouthwash.     

Protective effect of vitamin E supplements on experimental atherosclerosis is modest and depends on preexisting vitamin E deficiency

Vitamin E has failed to protect humans from cardiovascular disease outcome, yet its role in experimental atherosclerosis remains less clear. A previous study (Proc. Natl. Acad. Sci. USA 97:13830-13834; 2000) showed that vitamin E deficiency caused by disruption of the alpha-tocopherol transfer protein gene (Ttpa) is associated with a modest increase in atherosclerosis in apolipoprotein E gene deficient (Apoe(-/-)) mice. Here we confirm this finding and report that in Apoe(-/-)Ttpa(-/-) mice dietary alpha-tocopherol (alphaT) supplements restored circulating and aortic levels of alphaT, and decreased atherosclerosis in the aortic root to a level comparable to that seen in Apoe(-/-) mice. However, such dietary supplements did not decrease disease in Apoe(-/-) mice, whereas dietary supplements with a synthetic vitamin E analog (BO-653), either alone or in combination with alphaT, decreased atherosclerosis in Apoe(-/-) and in Apoe(-/-)Ttpa(-/-) mice. Differences in atherosclerosis were not associated with changes in the arterial concentrations of F(2)-isoprostanes and cholesterylester hydro(pero)xides, nor were they reflected in the resistance of plasma lipids to ex vivo oxidation. These results show that vitamin E at best has a modest effect on experimental atherosclerosis in hyperlipidemic mice, and only in situations of severe vitamin E deficiency and independent of lipid oxidation in the vessel wall.     

Dietary intake of antioxidant supplements modulate antioxidant status and heat shock protein 70 synthesis

The physiological effects and efficacy of dietary intake of antioxidant supplements in humans remains controversial. Experiments involving dietary, often high, intake of a single antioxidant or vitamin may be seriously flawed given the interactive nature of antioxidants in vivo. The present studies were conducted on individuals (35-60 years of age) taking a commercial antioxidant mixture in a double-blind, placebo-controlled, cross-over study. Intake was two capsules per day, for 4 weeks, with a 4-week washout period in between active dose or placebo. Intake of antioxidants was associated with little change in superoxide dismutase activity, but an increase in glutathione peroxidase was noted. Haemolysis of red blood cells (erythrocytes) induced by the free radical generator AAPH was significantly reduced in individuals on antioxidant supplements. In lymphocytes isolated from individuals taking supplements, there was a marked increase, as compared with individuals on placebo, in the synthesis of heat shock protein 70 (hsp70) following heat shock from 37 degrees C to 42.5 degrees C. We conclude that dietary intake of a mixed antioxidant supplement leads to modulation of cellular redox status resulting in decreased oxidative stress and increased ability of lymphocytes to mount a stress response.     

Dietary vitamin D3 supplements reduce demyelination in the cuprizone model

Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration. The mice received diets either deficient of (<50 IU/kg), or supplemented with low (500 IU/kg), high (6200 IU/kg) or very high (12500 IU/kg) amounts of vit D3. Cuprizone (0.2%) was added to the diet for six weeks, starting two weeks after onset of the experimental diets. Mouse brain tissue was histopathologically evaluated for myelin and oligodendrocyte loss, microglia/macrophage activation, and lymphocyte infiltration after six weeks of cuprizone exposure, and two weeks after discontinuation of cuprizone exposure. High and very high doses of vitamin D3 significantly reduced the extent of white matter demyelination (p = 0.004) and attenuated microglia activation (p = 0.001). No differences in the density of oligodendrocytes were observed between the diet groups. Two weeks after discontinuation of cuprizone exposure, remyelination was only detectable in the white matter of mice receiving diets deficient of or with low vitamin D3 content. In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration.     

Effects of dietary supplements on the space radiation-induced reduction in total antioxidant status in CBA mice

In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by proton, HZE-particle and gamma radiation in CBA mice. The results demonstrated that the plasma level of TAS was significantly decreased (P < 0.05) in CBA mice after exposure to a 50-cGy dose of radiation from HZE particles or a 3-Gy dose of radiation from protons or gamma rays. Diet supplementation with Bowman-Birk Inhibitor Concentrate (BBIC), L-selenomethionine (L-SeM), or a combination of N-acetyl cysteine, sodium ascorbate, co-enzyme Q10 (CoQ10), alpha-lipoic acid, L-SeM and vitamin E succinate could partially or completely prevent the reduction in the plasma level of TAS in CBA mice exposed to proton or HZE-particle radiation. The selected antioxidant combination with or without CoQ10 has a comparable protective effect on the gamma-radiation-induced drop in TAS in CBA mice. These results indicate that BBIC, L-SeM and the selected antioxidant combinations may serve as countermeasures for space radiation-induced adverse biological effects.     

Impact of iron and vitamin C-containing supplements on preterm human milk: in vitro

Stress due to reactive oxygen species (ROS) may lead to neonatal diseases, such as necrotizing enterocolitis and respiratory distress. Enteral supplements for premature infants (PREM) added to human milk (HM) to increase nutrient content may induce lipid oxidation due to free radical formation via Fenton chemistry. We hypothesized that ferrous iron and vitamin C-containing supplements added to HM in vitro cause oxidation of milk fats, affect intracellular redox balance, and induce DNA damage. Lipid peroxidation in HM was measured by FOX-2 and TBARS assays; fatty acid composition of supplemented HM was measured by gas chromatography. Two cell culture bioassays were used for assessing either intracellular oxidative stress or DNA damage: the former involved Caco-2BBe cells, a secondary differentiated cell line, and the latter utilized FHS-74 Int cells, a primary fetal small intestinal culture. Lipid oxidation products of HM increased after the addition of iron alone, iron and vitamin C, or iron and a vitamin C-containing supplement (Trivisol, TVS). A reduced content of mono and polyunsaturated fatty acids in HM was also observed. Iron, not iron+vitamin C, but iron+TVS induced significant intracellular oxidative stress in FHS-74 Int cells. In contrast, iron, either alone or in combination with TVS or vitamin C, increased DNA damage in Caco-2BBE cells. Iron supplementation may increase oxidative stress in PREM infants and should be given separately from vitamin C-containing supplements.     

Theoretical study of the pH-dependent antioxidant properties of vitamin C

Molecules acting as antioxidants capable of scavenging reactive oxygen species (ROS) are of utmost importance in the living cell. Vitamin C is known to be one of these molecules. In this study we have analyzed the reactivity of vitamin C toward the $ \cdot OH $ and $ \cdot OOH $ ROS species, in all acidic, neutral and basic media. In order to do so, density functional theory (DFT) have been used. More concretely, the meta-GGA functional MPW1B95 have been used. Two reaction types have been studied in each case: addition to the ring atoms, and hydrogen/proton abstraction. Our results show that $ \cdot OH $ is the most reactive species, while $ \cdot OOH $ displays low reactivity. In all three media, vitamin C reactions with two hydroxyl radicals show a wide variety of possible products.     

Vitamin D supplements and 25-hydroxy vitamin D concentrations in the elderly.

Serial 25-hydroxy vitamin D (25-OHD) concentrations were measured in long-stay geriatric patients treated with vitamin D. Comparison between a treatment and a control group showed that a daily dose of 500 IU vitamin D produced a significant increase in 25-OHD levels by two months. The supplement had a striking effect when the initial 25-OHD level was low and very little effect when it was high. 25-OHD levels in subjects on 2000 IU vitamin D daily were only marginally higher than those in subjects on 500 IU. A dose of 500 IU vitamin D daily should therefore produce adequate blood 25-OHD concentrations in most old people, and probably prevent most cases of osteomalacia in the elderly--though a large-scale study is needed to confirm this.     

Stress proteins as biomarkers of oxidative stress: effects of antioxidant supplements

The potential benefits to health of the supply of antioxidants, either through dietary intake or as supplements, is equivocal. There is a need to develop biomarkers that may act as monitors of cellular defense as influenced by antioxidant status. Thirty-two individuals participated in the project and 19 received supplements for 5 weeks in the form of a capsule containing a defined mixture of antioxidants. No change was noted in levels of superoxide dismutase and glutathione peroxidase following antioxidant supplementation. On the other hand, increase in total antioxidant status and decrease in malondialdehyde, protein carbonyl formation, and erythrocyte hemolysis were noted. In lymphocytes isolated from individuals receiving antioxidant supplements and subjected to a heat shock in the presence of the free radical generator 2, 2'-azobis-(2-amidinopropane)-dihydrochloride, enhanced synthesis of heat shock proteins hsp 105, hsp 90, hsp 70, and hsp 40 by contrast with decreased synthesis of heme oxygenase HO-1 (hsp 32) were noted. We conclude that antioxidant status modulates the synthesis of stress proteins.     

The extraordinary antioxidant activity of vitamin E phosphate

The antioxidant activities of RRR-vitamin E (VE), all-rac-vitamin E (all-rac-VE), trolox, RRR-vitamin E acetate (VEA), all-rac-vitamin E phosphate (VEP) and RRR-vitamin E succinate (VES) were compared. In this study, the rank order in the inhibition of lipid peroxidation (LPO) of VE and its derivatives was trolox>VE approximately all-rac-VE>VEA>VES. VE and trolox inhibited LPO in non-heated and heated rat liver microsomes. It has generally been accepted that this is due to scavenging of free radicals by these antioxidants, and during this protection the antioxidants are oxidized. VEA and VES have to be converted into VE by esterases to obtain antioxidant activity against LPO. VEP, however, had a potent antioxidant effect of its own without conversion to VE. In contrast to VE, VEP is not consumed during this protection. Of the compounds tested, VEP is the most potent in induction of hemolysis of erythrocytes. EPR experiments using the spin label 16-doxylstearic acid showed that VEP reduces membrane fluidity, in contrast to VE. This indicates that VEP acts as a detergent and forms a barrier that might inhibit the transfer of radicals from one polyunsaturated fatty acid to another. This new mechanism may form the basis for a new class of antioxidants.     

Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise

This study investigated the effects of antioxidant vitamin supplementation upon muscle contractile function following eccentric exercise and was performed double blind. Twenty-four physically active young subjects ingested either placebo (400 mg; n = 8), vitamin E (400 mg; n=8) or vitamin C (400 mg; n = 8) for 21 days prior to and for 7 days after performing 60 min of box-stepping exercise. Contractile function of the triceps surae was assessed by the measurement of maximal voluntary contraction (MVC) and the ratio of the force generated at 20 Hz and 50 Hz tetanic stimulation before and after eccentric exercise and for 7 days during recovery. Following eccentric exercise, MVC decreased to 75 (4) % [mean (SE); n = 24; P < 0.05] of the preexercise values and the 20/50 Hz ratio of tetanic tension from 0.76 (0.01) to 0.49 (0.03) [mean (SE); n = 24; P<0.05). Compared to the placebo group no significant changes in MVC were observed immediately post-exercise, though recovery of MVC in the first 24 h post-exercise was greater in the group supplemented with vitamin C. The decrease in 20/50 Hz ratio of tetanic tension was significantly less (P < 0.05) post-exercise and in the initial phase of recovery in subjects supplemented with vitamin C but not with vitamin E. These data suggest that prior vitamin C supplementation may exert a protective effect against eccentric exercise-induced muscle damage.     

The antioxidant efficiency of vitamin C is concentration-dependent

The inhibition of autoxidation of plasma lipids by vitamin C (ascorbic acid) has been studied. The ascorbate stoichiometric factor, n, i.e., the number of peroxyl radicals trapped by each ascorbate molecule, decreases as the concentration of ascorbate increases. This is attributed to the fact that ascorbate not only acts as a radical-trapping antioxidant, but can also undergo autoxidation. The data indicate that n----2.0 as [ascorbate]----0 and that n----0 as [ascorbate]----infinity. This concentration-dependent behaviour accounts for the wide variation of n values reported in the literature. It is suggested that this autoxidative destruction of ascorbate may play a role regulating its concentration in blood plasma.     

The effect of vitamin B6 supplements on development of seizures in the gerbil, Meriones unguiculatus.

To see if a Vitamin B6 deficiency is responsible for seizure-proneness in the gerbil, $\text{Meriones unguiculatus}$, a diet supplemented with 0.5mg of pyridoxine per gram of Purina Lab Chow was fed to 8 experimental (E) mated pairs and their litters while 8 control (C) pairs and their litters were fed Purina Lab Chow which contains .004mg per gram of pyridoxine. All litters were tested for seizures every 2 weeks from 2 through 7 mos. of age once a month in a standard (SS) test cage and 2 weeks later in a clean home cage (CC) — and again at 1 yr in the SS cage. There were no differences on any of the measures between E and C litters. Significantly more seizures were elicited in the SS than in the CC tests, and the SS test became increasingly more effective with age. It was concluded that gerbil seizures were not due to a Vitamin B6 deficiency and that some age-related process might be a productive area for future investigation.     

Effect of phytyl side chain of vitamin E on its antioxidant activity

Inhibition of the oxidation of methyl linoleate and soybean phosphatidylcholine in homogeneous solution and in aqueous dispersion by four chain-breaking antioxidants, vitamin E (alpha-tocopherol), 2,2,5,7,8-pentamethyl-6-chromanol, 2,6-di-tert-butyl-4-methylphenol, and stearyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, was studied to examine the effect of the phytyl side chain of vitamin E on its antioxidant activity. These four antioxidants exerted similar antioxidative activities. They were also effective as antioxidants in protecting the oxidation of soybean phosphatidylcholine liposomes in water dispersion. However, when they were incorporated into dimyristoyl phosphatidylcholine liposomes, only 2,2,5,7,8-pentamethyl-6-chromanol and 2,6-di-tert-butyl-4-methylphenol could suppress the oxidation of soybean phosphatidylcholine liposomes dispersed in the same aqueous system. It was concluded that the antioxidative properties of vitamin E and its model without the phytyl side chain are quite similar within micelles and liposomes as well as in homogeneous solution but that the phytyl side chain enhances the retainment of vitamin E in liposomes and suppresses the transfer of vitamin E between liposomal membranes.     

维生素C对镉负荷小鼠睾丸抗氧化功能的影响*

目的: 分析镉(Cd)负荷不同时间对小鼠睾丸抗氧化酶的影响及维生素C(VC)的保护作用。方法: 清洁级雄性昆明小鼠72只分为4组(n=18):对照组、Cd组(CdCl₂ 3 mg/kg)、VC组(200 mg/kg)、VC(200 mg/kg)+ Cd(CdCl₂ 3 mg/kg)组,每日染毒1次,染毒1 d和3 d及同时补充VC保护,第1日和第3日染毒24 h后,每组取半数小鼠称重,取血清和睾丸组织;检测睾丸脏器系数,血清和睾丸组织丙二醛(MDA)、超氧化物歧化酶(SOD),及睾丸组织谷胱甘肽过氧化物酶(GSH-Px)、还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)及总谷胱甘肽(T-GSH)。结果: 与对照组比较,Cd组1 d和3 d小鼠体重和睾丸脏器系数下降;染毒3 d,Cd组小鼠血清SOD显著降低、MDA显著升高(P＜0.05);Cd组1 d小鼠睾丸的SOD、GSH-Px、T-GSH及GSH/GSSG显著升高(P＜0.05),而3 d的上述指标均显著降低(P＜0.05),Cd组1 d和3 d MDA水平均显著升高(P＜0.05);VC处理后减轻的程度有所降低。与Cd组比较,VC+ Cd组血清SOD和MDA水平在染毒3 d变化有显著性差异(P＜0.05);VC+ Cd组在染毒1 d和3 d,小鼠睾丸的SOD、GSH-Px、T-GSH及GSH/GSSG水平变化有显著性差异(P＜0.05),VC+ Cd组在染毒3 d睾丸的MDA水平显著降低(P＜0.05)。与Cd组1 d比较,染毒3 d小鼠的血清SOD水平显著降低(P＜0.05),睾丸指标变化也有显著性差异(P＜0.05)。结论: VC处理可在一定程度上改善镉负荷小鼠的抗氧化功能,对睾丸氧化损伤具有保护作用。     

Vitamin E deficiency and vitamin C supplements: exercise and mitochondrial oxidation

The effects of dietary antioxidant vitamins E and C on exercise endurance capacity and mitochondrial oxidation were investigated in rats. The endurance capacity of both vitamin E-deficient and vitamin C-supplemented, E-deficient rats was significantly (P less than 0.05) lower (38.1 and 33.6%, respectively) than control animals. Compared with the normal and vitamin E-deficient rats, there was a significant (P less than 0.05) increase in the concentration of vitamin C in blood and liver of the vitamin E-deficient, C-supplemented animals. Hence dietary vitamin C supplementation does not prevent the inhibition of exercise endurance capacity or increased hemolysis seen in vitamin E deficiency. The mitochondrial activities for the oxidation of palmitoyl carnitine and alpha-ketoglutarate were significantly (P less than 0.05) decreased by a single bout of exercise in brown adipose tissue but not in muscle, heart, or liver from vitamin C-supplemented, E-deficient groups of rats when compared with the activities in the tissue from the same group of rats killed at rest. Similar results were also seen in brown adipose tissue from vitamin E-deficient rats. The results suggest a tissue-specific role for vitamins E and C in substrate oxidation and show that the poor endurance capacity of vitamin E-deficient rats cannot be attributed to any changes in the mitochondrial activity in skeletal or cardiac muscles. It is also concluded that vitamin C supplementation, at least at the dose employed in the present study, cannot counteract the detrimental effects associated with vitamin E deficiency.     

On the use of acridinium indicators for the chemiluminescent determination of the total antioxidant capacity of dietary supplements

Acridinium salts, due to their chemiluminogenic properties, have found several applications in biomedical analysis as labels and indicators, where the assessment of emission intensity is used for the end‐point detection. This work presents the use of chemiluminescent indicators in the form of selected acridinium esters in order to determine the antioxidant properties of exemplary formulations, namely quercetin, vitamin C and the dietary supplement, Apiextract. The principle of measurements is based on a change in the kinetics of emission decay derived from the acridinium cations in alkaline solutions of hydrogen peroxide in the presence of an antioxidant (the analyte). The proposed system makes a beneficial alternative to related methods, which mostly rely on the assessment of emission efficiency and use the luminometric standard luminol – due to superior parameters of acridinium chemiluminescence, among others ‐ high temporary emission efficiency. The features of the proposed method are manifested by a shorter time period of analysis and lower background signals associated with the environmental influences, as compared to typical approaches. The chromatographic (RP‐HPLC) analyses of the substrates and products generated during chemiluminogenic oxidation of acridinium cations under assay conditions are also presented.     

Fibrinogen is a co-antioxidant that supplements the vitamin E analog trolox in a model system

Objective: It appears that the atherosclerotic plaque is a prooxidant environment where some molecules that are normally antioxidants, including vitamins C and E, may act as prooxidants that contribute to atherosclerosis by oxidizing LDL. Some molecules can act as co-antioxidants to eliminate this prooxidant effect by recycling or other mechanisms of supplementation. Fibrinogen and other acute phase proteins found in the plaque are antioxidants. We hypothesized that fibrinogen can act as a co-antioxidant to supplement vitamin E thereby eliminating its oxidative effect under prooxidant conditions. We tested a model system for this hypothesis using the vitamin E analogue Trolox in a cell free system.

Methods: LDL was oxidized using 5 umol/l copper. Antioxidant conditions were achieved by adding the antioxidants immediately with LDL, while prooxidant conditions were created by adding antioxidants after a 40 min delay. Oxidation was monitored as the lag phase at 234 nm.

Results: Under antioxidant conditions, the protective effect of fibrinogen and Trolox combined together were about equal to the sum of the anitioxidant effects of each alone (additive), while under prooxidant conditions the combined protection was 54-200% greater (synergistic). These effects were different than those of vitamin C with Trolox in that under antioxidant conditions fibrinogen and Trolox were additive while vitamin C and Trolox showed strong synergistic effects, and in that unlike vitamin C and Trolox fibrinogen showed no prooxidant tendencies under prooxidant reaction conditions.

Conclusions: The data indicated that fibrinogen did act as a co-antioxidant to supplement Trolox and eliminate its prooxidant effect, most probably, by directly quenching the phenoxyl radical, because unlike vitamin C, fibrinogen did not appear to recycle vitamin E. But fibrinogen may act as a universal antioxidant, since unlike Trolox and vitamin C, it showed little tendency toward becoming a prooxidant.