Effects Of Antioxidant Vitamins Research Articles

OC93: Effect of antioxidant vitamins in the prevention of pre‐eclampsia in women with abnormal uterine artery Doppler during the second trimester of pregnancy

OC93: Effect of antioxidant vitamins in the prevention of pre‐eclampsia in women with abnormal uterine artery Doppler during the second trimester of pregnancy

Effects of antioxidant vitamins on molecular regulators involved in lung hypoplasia induced by nitrofen

Introduction Oxidant herbicide nitrofen (2,4-dichloro-4′-nitrodiphenyl ether) induces in rat embryos congenital diaphragmatic hernia (CDH) with lung hypoplasia. The present study aims at examining whether antioxidant vitamins A, E, and C reverse the effects of the teratogen in the lungs of exposed rats and how they modify the expression of molecular regulators known to be involved in their pathogenesis. Materials and Methods Wet lung weight–body weight ratio, total DNA, and total protein were determined. Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3 β (HNF-3 β), and surfactant protein B (SP-B) proteins were measured by immunoblot assay in lung homogenates from rat fetuses exposed in utero to either nitrofen 100 mg intragastrically or vehicle. The coexpression of these factors in the alveolar epithelium was demonstrated by immunohistochemistry. The effects of the addition of vitamins A, C, and E were assessed by comparison with analysis of variance. Results Nitrofen decreased lung weight, total DNA, and total protein. The addition of antioxidant vitamins had no effect on lung weight, but increased DNA and protein contents. TTF-1, HNF-3 β, and SP-B proteins were decreased in lung homogenates of exposed rats with CDH. The addition of antioxidant vitamins nearly normalized these values. Conclusions The effects of nitrofen in fetal rat lungs are reversed in part by antioxidant vitamins by upregulating the expression of TTF-1, HNF-3 β, and SP-B. This approach could help to develop transplacental prenatal interventions for CDH.

Effects of Nitrofen and Vitamins A, C and E on Maturation of Cultured Human H441 Pneumocytes

Background/Aim: Nitrofen (2,4-dichloro-4´-nitrodiphenyl ether), a teratogen with oxidant properties, induces congenital diaphragmatic hernia (CDH) with lung hypoplasia and delayed lung development and maturation in rat embryos. Several phenotypic features of the alveolar epithelium including surfactant proteins A and B synthesis and its regulation by transcription factors are reproduced in cultured human H441 pneumocytes. The aim of the present study was to test whether vitamins A, E and C with anti-oxidant properties were able to recover the expression of such regulators in an in vitro setting. Materials and Methods: Cultured human H441 pneumocytes were treated with nitrofen with or without additional exposure to vitamins A, E and C. Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3-β (HNF-3β) and hepatocyte nuclear factor 3-β surfactant protein B (SP-B) mRNAs were measured by real-time polymerase chain reaction (RT-PCR). The cells were also immunohistochemically stained for assessment of proliferation (PCNA) and apoptosis (bis-benzimide) status and SP-B and TTF-1 protein expressions. Results were compared by ANOVA with a significant threshold of 5%. Results: Nitrofen severely decreased TTF-1, HNF-3β and SP-B mRNA expression by H441 pneumocytes in culture. Addition of vitamin E normalized the levels of the three transcripts, while vitamin A normalized only those of TTF-1 and SP-B mRNA. Vitamin C was significantly beneficial only for SP-B transcript. Nitrofen decreased proliferation and TTF-1 and SP-B protein expressions with no apparent effect on apoptosis. Additional exposure to vitamins A, C or E rescued near normal values. Conclusions: The changes induced by nitrofen in cultured H441 human pneumocytes are reverted in part by anti-oxidant vitamins by upregulating TTF-1, HNF-3β and SP-B and stimulating proliferation and maturity in nitrofen-treated cells. These effects of anti-oxidant vitamins could be of some interest for developing new transplacental therapeutic strategies aimed at improving lung development and maturation in fetuses with CDH.

Impact of Coronary Endothelial Function on the Progression of Cardiac Transplant–associated Arteriosclerosis: Effect of Anti-oxidant Vitamins C and E

Excessive vascular oxidant stress has been implicated in cardiac transplant-associated arteriosclerosis (TxAA). In a recent placebo-controlled study of 40 cardiac transplant recipients, vitamin C 500 mg twice a day and vitamin E 400 IU twice a day for 1 year retarded the progression of TxAA, as assessed by intravascular ultrasound (IVUS). Endothelial dysfunction is a key feature of TxAA and reflects oxidant stress. We hypothesized that coronary endothelial dysfunction portends greater TxAA progression and a larger therapeutic response to anti-oxidant vitamins. In this pre-specified analysis, the 40 cardiac transplant recipients were categorized according to normal or abnormal coronary endothelial vasomotor function at baseline, as assessed by acetylcholine (10(-8) to 10(-6) mol/liter). The effect of anti-oxidant vitamins within these two groups of patients was assessed by the change in intimal index over 1 year using IVUS. With placebo (n = 21), the increase in intimal index was greater in the presence vs absence of endothelial dysfunction (11 +/- 3% vs 5 +/- 1%, p < 0.05). Among patients with endothelial dysfunction (n = 21), the intimal index increased 11 +/- 3% with placebo, but decreased -1 +/- 2% with vitamins (p = 0.002). Among patients with normal endothelial function (n = 14), the intimal index increased 5 +/- 1% with placebo and 1 +/- 1% with vitamins (p < 0.05). Endothelial dysfunction indicates rapid TxAA progression, even in the statin era. Although anti-oxidant vitamins reduce disease progression in patients with normal or abnormal endothelial function, the magnitude of benefit is larger in patients with endothelial dysfunction.

Dual role of vitamin C in an oxygen-sensitive system: Discrepancy between DNA damage and dell death

Although vitamin C is considered to act both as pro-oxidant and antioxidant, the mechanisms underlying these actions are still unclear. Using the oxygen-sensitive system of a strict anaerobe, Prevotella melaninogenica, we investigated both the pro-oxidant and antioxidant mechanisms of vitamin C. In the presence of vitamin C, the 8-hydroxydeoxyguanosine (8OHdG) formation induced by oxygen exposure was enhanced, probably due to the action of vitamin C on hydrogen peroxide generated during oxygen exposure: while catalase almost completely suppressed the enhancing effect of vitamin C, 8OHdG formation induced by hydrogen peroxide was enhanced by vitamin C. By contrast, the presence of vitamin C inhibited bacterial cell death, membrane damage, and lipid peroxidation induced by oxygen exposure. Sodium azide showed similar effects to vitamin C, thus the antioxidant action of vitamin C may be due to its quenching of the singlet oxygen generated in this system. Both the pro-oxidant and antioxidant effects of vitamin C were observed only in acidic conditions.

Effects of Antioxidant Vitamins on Glutathione Depletion and Lipid Peroxidation Induced by Restraint Stress in the Rat Liver

Stress as a cofactor has been reported to affect the progression and severity of several diseases. The influence of stress on the liver is of interest from the clinical point of view because stress plays a potential role in aggravating liver diseases in general and hepatic inflammation in particular, probably through generation of reactive oxygen species. The present study was undertaken to investigate the potential of the antioxidant vitamins A (retinol), E (tocopherol) and C (ascorbic acid) individually and in combination (vitamin E + C) to modulate restraint stress-induced oxidative changes. These effects were determined by measuring changes in hepatic levels of free radical scavenging enzymes such as superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase, as well as levels of total glutathione (GSH), malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Immobilisation was achieved by placing the animals in wire mesh cages of their size. The rats were orally administered vitamins A, E and C individually and in combination (E + C) prior to and after 6 hours of immobilisation stress exposure. The hepatic levels of SOD, GST, catalase, GSH and MDA were determined by spectrophotometric methods. Liver SOD activity was assayed by monitoring the amount of enzyme required to inhibit autoxidation of pyrogallol by 50%. Hepatic GST was monitored by following the increase in absorbance at 340 nm of CDNB-GSH conjugate generated due to GST catalysis between GSH and CDNB. Catalase activity in liver tissues was determined using peroxidase as the substrate. Lipid peroxidation was measured by determining the level of thiobarbituric acid reactive substances. ALT and AST were determined by commercial kits. Six hours of immobilisation stress caused a decrease in liver levels of SOD (p = 0.001), catalase (p = 0.031), GST (p = 0.021) and GSH (0.013), while levels of MDA (p = 0.0015), AST (p = 0.05) and ALT (p = 0.046) were increased compared with non-stressed control rats. Both pre-vitamin stress and post-vitamin stress treatments either alone or in combination were associated with increased normalisation of these parameters towards control values, with post-vitamin treatment being the more effective of the two. Vitamins E and C individually were found to be more effective in restoring the endogenous antioxidant system than vitamin A. The combined vitamin (E + C) post-stress treatment was found to be effective but not additive in combating hepatic oxidative stress. The beneficial effects of these vitamin treatments were also reflected in reversions of altered AST and ALT levels towards their control values. Vitamins E or C alone or in combination can be given as prophylactic/therapeutic supplements for combating scavenging free radicals generated in liver tissue. This approach may reduce oxidative stress caused by diseases such as cirrhosis.

Beneficial effects of selected antioxdants in experimental diabetes

The antioxidant effects of Vitamins C, E and N-acetyl-L-cysteine (N) on glucose disposal, reduced glutathione (GSH), malonyldialdehyde (MDA) and antioxidant enzymes glutathione peroxidase (GPX) and glutathione reductase (GRT) in the levels of streptozotocin-induced diabetic rats was investigated. Glucose tolerance test (GTT) levels of untreated rats (group 1) were relatively elevated in STZ rats compared with rats fed antioxidant, supplemented diets, (Vit. C + E, group 3) and (N+C+E, group 4), although both antioxidant supplemented and untreated rats did not dispose off any appreciable quantity of glucose. A significant level (P

Antioxidant effect of EGb 761 on hydrogen peroxide‐induced lipoperoxidation of G‐6‐PD deficient erythrocytes

In order to reduce the haemolytic susceptibility of glucose-6-phosphate dehydrogenase (G-6-PD) deficient erythrocytes, Ginkgo biloba extract (EGb 761) and vitamin E (vit E) were used as antioxidant agents and their effects compared. The erythrocyte suspensions from control and G-6-PD deficient patients were subjected to hydrogen peroxide (H2O2) incubation for 1 h. The produced thiobarbituric acid reactive substance (TBARS) levels measured as nmol/g Hb were compared with those of the erythrocytes administered 250 microg/mL EGb 761 or vit E previously or concomitantly with H2O2. Preincubation with EGb 761 reduced the TBARS levels from 317.14 +/- 25.27 to 160.09 +/- 21.97 nmol/g Hb in controls and from 348.24 +/- 7.79 to 205.60 +/- 14.22 nmol/g Hb in deficient erythrocytes. Concomitant application of EGb 761 with H2O2 resulted in similar but less reduction. The antioxidative effects of vitamin E were comparable to those of EGb 761. Contrary to the results obtained from oxidant conditions, the antioxidant characteristics of EGb 761 and vitamin E were not observed when they were applied directly to the erythrocytes without oxidative stress. The findings demonstrate that irrespective of administration time, EGb 761 significantly reduced TBARS levels in the erythrocytes of control and G-6-PD deficient patients subjected to oxidative stress.

Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium

Aluminium has the potential to be neurotoxic in humans and animals, and is present in many manufactured foods and medicines and is also added to drinking water for purification purposes. Therefore, the present study was carried out to investigate (1) the alterations in biochemical parameters, free radicals and enzyme activities induced by aluminium chloride (AlCl 3) in plasma and different tissues of male rats, and (2) the role of vitamin E (VE) and selenium in alleviating the negative effects of aluminium. VE plays an important role as an antioxidant and is consequently expected to protect tissues from damage caused by reactive oxygen metabolites. Selenium is also generally recognized to be a trace mineral of great importance for human health, protecting the cells from the harmful effects of free radicals. Seven rats per group were assigned to one of six treatment groups: 0 mg VE, 0 mg Se and 0 mg AlCl 3/kg body weight (BW) (control); 100 mg VE/kg BW; 200 μg Se kg BW; 34 mg AlCl 3/kg BW (1/25 LD 50); 34 mg AlCl 3 plus 100 mg VE/kg BW; 34 mg AlCl 3 plus 200 μg Se/kg BW. Rats were orally administered their respective doses every other day for 30 days. Evaluations were made for lipid peroxidation, enzyme activities and biochemical parameters. Results obtained showed that AlCl 3 significantly ( p<0.05) induced free radicals (thiobarbituric acid-reactive substances) and decreased the activity of glutathione S-transferase (GST) and the levels of sulphydryl groups (SH groups) in rat plasma, liver, brain, testes and kidney. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, and phosphorylase activities were significantly decreased in liver and testes due to AlCl 3 administration, while the activities of these enzymes were significantly increased in plasma. In addition, plasma, liver, testes and brain lactate dehydrogenase activities were significantly increased. On the contrary, the activity of acetylcholinesterase was significantly decreased in brain and plasma. Al treatment caused a significant decrease in plasma total protein (TP), albumin and total lipids (TL), and increased the concentrations of glucose, urea, creatinine, bilirubin and cholesterol. VE or Se alone significantly decreased the levels of free radicals, TL, cholesterol, urea and bilirubin, and increased the activity of GST, and SH groups, TP and albumin, while the rest of the tested parameters were not affected. VE or Se in combination with Al partially or totally alleviated its toxic effects on the studied parameters. In conclusion, VE and Se have beneficial effects and could be able to antagonize Al toxicity.

Superoxide anion overproduction in sepsis: effects of vitamin e and simvastatin.

Oxidative stress during sepsis induces tissue damage, leading to organ dysfunction and high mortality. The antioxidant effects of vitamin E have been reported in several diseases, but not in sepsis. Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress. Therefore, we evaluated superoxide anion (O2- degree) production and ex vivo effects of vitamin E and simvastatin in sepsis. Fourteen healthy volunteers, 14 intensive care unit (ICU) nonseptic, and 14 ICU patients with sepsis were included in this prospective study. Plasma cholesterol, triglyceride, and vitamin E levels were determined by routine laboratory tests. Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation. Effects of vitamin E and simvastatin on O2- degree production was investigated ex vivo. Luminescence was indexed to the leukocyte count. We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line. The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers. The O2- degree production was significantly higher in the group of septic patients than in the others, regardless of the polymorphonuclear leukocyte count. Vitamin E and simvastatin induced ex vivo an inhibition of O2- degree production of 20% and 40% respectively. In vitro, simvastatin inhibited phorbol myristate acetate-induced- O2- degree production by monocytes through NADPH oxidase inactivation. We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2- degree. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation.

P2-017 The effects of antioxidant vitamin E upon lipid peroxidation and catalase activity in rat brain treated with cyclophosphamide

P2-017 The effects of antioxidant vitamin E upon lipid peroxidation and catalase activity in rat brain treated with cyclophosphamide

Impact of Vitamin E supplementation on lipoprotein peroxidation and composition in Type 1 diabetic patients treated with Atorvastatin

Objective: To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment. Research Design and Methods: T1DM patients with high cholesterol received Atorvastatin 20 mg with either placebo (group AP, n = 11) or d-α-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation at inclusion and after 3 and 6 months. Results: Serum cholesterol and triglycerides decreased to the same extent (29 and 21% respectively) in both groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE ( P < 0.0001, between-group comparison by repeated measures ANOVA) but relative to lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in AP and did not change in AE ( P = 0.02). The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE ( P = 0.028). Plasma malondialdehyde decreased by 35% in both groups ( P = 0.002) but not when adjusted for lipids. Conclusions: In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs. These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin.

Endothelial Dysfunction, Vascular Damage and Clinical Events

Impaired endothelial function due to reduced nitric oxide availability secondary to an augmented production of oxidative stress has been associated with an increased risk of cardiovascular events in patients with coronary artery disease. Therefore, improvement of endothelial function through antioxidant therapy might be an important therapeutic approach for the prevention of cardiovascular morbidity and mortality. Available evidence indicates that acute high-dose ascorbic acid (vitamin C) improves endothelial function in high-risk patients. In contrast, results from clinical trials on the effect of long-term antioxidant therapy are contradictory. This discrepancy could be due to different experimental designs, vascular areas, diseases, range of doses and concomitant drugs utilised. The possibility that antioxidant vitamins can reduce cardiovascular damage and prevent cardiovascular events has been investigated in several studies. While observational studies suggested an inverse relationship between antioxidant vitamin intake and progression of atherosclerotic lesions, controlled clinical studies showed no effect of antioxidant vitamins on post-percutaneous transluminal coronary angioplasty stenting restenosis, coronary and carotid atherosclerotic lesions. Controlled studies evaluating the effect of antioxidant vitamins, in particular tocopherol (vitamin E), on cardiovascular events showed no beneficial effect in six of eight trials, although data concerning both the presence or absence of benefit in particular patients and the type of cardiovascular events were discordant. Overall, while these data indicated that at this time antioxidant vitamins are not to be recommended for the prevention of cardiovascular events, they did not contradict the hypothesis that antioxidant therapy should still be considered an important tool for prevention-regression of atherosclerosis and prevention of cardiovascular events. However, this potential benefit needs to be confirmed by future controlled clinical studies using new antioxidant substances with optimal pharmacokinetics and pharmacodynamics, in order to achieve high bioavailability and a documented dose-dependent antioxidant effect.

Vitamin E protects porcine but not bovine cultured aortic endothelial cells from oxygen-derived free radical injury due to hydrogen peroxide.

The antioxidative effects of vitamin E (VE) are well known and have been demonstrated in in vitro studies. Since we previously observed that dextran sulfate was markedly more protective of porcine versus bovine aortic endothelial cells when damaged by hydrogen peroxide (H2O2), our objectives were to determine if a similar species difference could be observed with VE. The effects of VE or Trolox (a more water-soluble VE) against oxygen-derived free radical (OFR) injury produced by H2O2 was studied in porcine aortic endothelium (PAE) vs. bovine aortic endothelium (BAE) and bovine brain microvessel endothelium (BBME). VE or Trolox was added to culture medium for at least 24 h prior or immediately prior to H2O2 addition. In PAE, pretreatment with VE dissolved in either ethanol (VE-EtOH) or Tween 20 (VE-Tween 20), or Trolox dissolved in DMSO (Trolox-DMSO) was protective, shown by increased percent viable cells and reduced lactate dehydrogenase (LDH) release. EtOH, Tween 20 or DMSO alone was protective in PAE although DMSO or Tween 20 alone was less effective than when added with VE. VE-Tween 20 or Trolox-DMSO protected PAE when added just prior to H2O2 injury, but protection was significantly less than with pretreatment. DMSO immediately prior to H2O2 injury had no protective effect. Tween 20 immediately prior resulted in complete cell death. In BAE and BBME, pretreatment with VE-EtOH, EtOH, Trolox-DMSO, or DMSO alone had little or no protective effect. Pretreatment with VE-Tween 20 or Tween-20 alone was protective of BAE with Tween 20 being more effective than VE-Tween 20 suggesting that Tween 20 was the protective agent. These studies show that the protective effects of VE and Trolox as well as DMSO, EtOH, and Tween-20 are species dependent.

Testing endothelial vasomotor function: nitric oxide, a multipotent molecule.

The initial description in 1980 by Furchgott and Zawadzki1 of endothelium-derived vasodilator factor has stimulated more than 2 decades of intense research to delineate the basic biology of the endothelium and its importance in the clinical setting.2 Endothelium-derived vasodilator factor has been identified as nitric oxide (NO).2 It is formed in endothelial cells from the amino acid l-arginine by endothelial isoform of NO synthase (eNOS), which is the product of the NOS3 gene.2,3 In addition to producing NO constitutively, the enzyme may be stimulated to increase NO synthesis by a variety of physiological agonists, shear stress, and pharmacological agents. Although discovered as a vasodilator, NO mediates many of the protective functions of the endothelium.4 It limits vascular recruitment of leukocytes by inhibiting the expression of proinflammatory cytokines, chemokines, and leukocyte adhesion molecules.2,4 It inhibits vascular smooth muscle proliferation and platelet adhesion and aggregation.2,4 NO also inhibits the production of tissue factor, a molecule that plays a critical role in the propensity of disrupted atherosclerotic plaques to cause intravascular thrombosis.5 In the setting of risk factors and experimental atherosclerosis, loss of the biological activity of endothelium-derived NO is accompanied by other alterations in endothelial phenotype that further increase the propensity for vasoconstriction, thrombosis, inflammation, and cellular proliferation in the vascular wall.6 Thus, endothelial dysfunction has the potential to contribute to key events in the course of human atherosclerosis. The experimental observations of Furchgott and others have stimulated translational research to elucidate the importance of endothelium-dependent vasodilation in human coronary atherosclerosis. Accordingly, Ludmer and colleagues7 administered the endothelium-dependent dilator acetylcholine into the coronary arteries of subjects undergoing cardiac catheterization. Acetylcholine induced dilation of normal epicardial coronary arteries but induced abnormal vasoconstriction, indicative of endothelial dysfunction, in patients with angiographic evidence of …

Some histologic and biochemical evidence for mitigation of cyanide-induced tissue lesions by antioxidant vitamin administration in rabbits

The effect of antioxidant vitamins on cyanide-induced tissue damage was investigated in New Zealand White rabbits using a combination of colorimetric, spectrophotometric, enzymatic, gravimetric and histological methods. Three groups of rabbits (six per group) were used in a 4-week feeding experiment. One group received pure grower's mash, while a second group was fed mash containing 400 ppm inorganic cyanide. The third group received daily oral doses of vitamins A, C and E, in addition to mash and 400 ppm cyanide. There were significant decreases (P<0.05) in activities of superoxide dismutase (SOD), catalase and alkaline phosphatase (AP) in the liver, lung and kidney of the two groups given cyanide, but the decreases were significantly lower (P<0.05) in the group fed antioxidant vitamins. In addition, the antioxidant vitamin supplementation led to marked reductions in the severity of histopathological degeneration in these tissues. These results strongly suggest that cyanide-induced tissue lesions may be relieved by adequate intake of antioxidant vitamin supplements.

Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400 IU/day (group B), vitamin C 2g/day plus vitamin E 800 IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.

Comparative study of antioxidant defence mechanisms in marine fish fed variable levels of oxidised oil and vitamin E

The aim of the study was to compare theantioxidant systems in juvenile marine fish ofcommercial importance to European aquaculture,namely turbot (Scophthalmus maximus),halibut (Hippoglossus hippoglossus) andgilthead sea bream (Sparus aurata). Thepresent dietary trial was specifically designedto investigate the antioxidant effects ofvitamin E under moderate oxidising conditions,including high dietary levels of highlyunsaturated fatty acids and the feeding ofoxidised oils. The objective was to induce astressful pro-oxidant status to enablecharacterisation of the biochemical responsesto peroxidative stress without causingunnecessary suffering to the experimentalanimals or high mortalities during the trials. Both sea bream and turbot showed excellentgrowth, whereas growth was poorer in halibut.Dietary oxidised oil significantly reducedgrowth in turbot and especially in halibut, butnot in sea bream. Vitamin E improved growth insea bream fed oxidised oil but not in turbot orhalibut. However, vitamin E supplementationappeared to improve survival in all threespecies. In sea bream and turbot, liverantioxidant defence enzyme activities weregenerally increased by feeding peroxidised oiland reduced by vitamin E. Conversely, inhalibut, the liver antioxidant defence enzymeactivities were not increased by feedingperoxidised oil and only superoxide dismutasewas reduced by feeding vitamin E. Consistentwith these data, feeding oxidised oil increasedlipid peroxidation products in halibut, butgenerally not in sea bream or turbot.Furthermore, lipid peroxidation products weregenerally reduced by dietary vitamin E in bothsea bream and turbot, but not in halibut. Therefore, halibut liver antioxidant defenceenzymes did not respond to dietary oxidised oilor vitamin E as occurred in turbot and,especially sea bream. This resulted inincreased levels of lipid peroxides in halibutcompared to turbot and sea bream in fish givendietary oxidised oil. In addition, supplementalvitamin E did not reduce lipid peroxides inhalibut as it did in turbot and sea bream. Theincreased peroxidation stress in halibut mayaccount for their poorer growth and survival incomparison to turbot and especially sea bream.Halibut were reared at a lower temperature,although relatively high for halibut, thaneither turbot or sea bream but they were alsoslightly younger/smaller fish and possibly,therefore, more developmentally immature, andeither or all of these factors may be importantin the lack of response of the liver enzymes inhalibut.

Mutagenicity of Food-Derived Carcinogens and the Effect of Antioxidant Vitamins

The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, β-carotene, ascorbic acid (vitamin C), and α-tocopherol (vitamin E), on food-borne mutagens/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins. Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt MF. Vitamin E was the most effective at decreasing Hprt MF. In addition, we determined whether carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of β-carotene and vitamin C without the carcinogen resulted in an increase (P < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone. Although the mechanisms of action of the antioxidants remain to be determined, the results indicate that dietary-derived HCA treatment induced MF in rat lymphocytes and suggest that antioxidants in food or taken as supplements could, in part, counteract such mutagenic activities.

Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review.

Do antioxidant vitamins, in regular food or as food supplements, protect against myocardial infarction and stroke? In this systematic literature review on the effects of antioxidant vitamins in the primary prevention of cardiovascular disorders, studies with ischaemic heart disease, stroke or combined cardiovascular events as end-points have been included. Studies on the effects of antioxidant vitamins on intermediary end-points (such as blood lipids and blood pressure) and as secondary prevention in patients with manifest cardiovascular disease are reviewed in a conventional manner. In observational studies (case-control or cohort design), people with high intake of antioxidant vitamins by regular diet or as food supplements generally have a lower risk of myocardial infarction and stroke than people who are low-consumers of antioxidant vitamins. The associations in observation studies have been shown for carotene, ascorbic acid as well as tocopherol. In randomized controlled trials, however, antioxidant vitamins as food supplements have no beneficial effects in the primary prevention of myocardial infarction and stroke. Serious adverse events have been reported. After an initial enthusiasm for antioxidants in the secondary prevention of cardiovascular disease, recent reports from of several large randomized trials have failed to show any beneficial effects. Thus, the apparent beneficial results of high intake of antioxidant vitamins reported in observational studies have not been confirmed in large randomized trials. The discrepancy between different types of studies is probably explained by the fact that supplement use is a component in a cluster of healthy behaviour. Antioxidant vitamins as food supplements cannot be recommended in the primary or secondary prevention against cardiovascular disease.