Honest sexual signalling mediated by parasite and testosterone effects on oxidative balance

Extravagant ornaments evolved to advertise their bearers'' quality, the honesty of the signal being ensured by the cost paid to produce or maintain it. The oxidation handicap hypothesis (OHH) proposes that a main cost of testosterone-dependent ornamentation is oxidative stress, a condition whereby the production of reactive oxygen and nitrogen species (ROS/RNS) overwhelms the capacity of antioxidant defences. ROS/RNS are unstable, very reactive by-products of normal metabolic processes that can cause extensive damage to key biomolecules (cellular proteins, lipids and DNA). Oxidative stress has been implicated in the aetiology of many diseases and could link ornamentation and genetic variation in fitness-related traits. We tested the OHH in a free-living bird, the red grouse. We show that elevated testosterone enhanced ornamentation and increased circulating antioxidant levels, but caused oxidative damage. Males with smaller ornaments suffered more oxidative damage than those with larger ornaments when forced to increase testosterone levels, consistent with a handicap mechanism. Parasites depleted antioxidant defences, caused oxidative damage and reduced ornament expression. Oxidative damage extent and the ability of males to increase antioxidant defences also explained the impacts of testosterone and parasites on ornamentation within treatment groups. Because oxidative stress is intimately linked to immune function, parasite resistance and fitness, it provides a reliable currency in the trade-off between individual health and ornamentation. The costs induced by oxidative stress can apply to a wide range of signals, which are testosterone-dependent or coloured by pigments with antioxidant properties.     

Relationship between oxidative stress and circulating testosterone and cortisol in pre-spawning female brown trout

Reproduction in vertebrates is an energy-demanding process that is mediated by endogenous hormones and potentially results in oxidative stress. The primary aim of this study was to quantify the relationship between oxidative stress parameters (antioxidant capacity and levels of reactive oxygen metabolites) and circulating testosterone and cortisol in a common and widespread teleost fish, the brown trout (Salmo trutta, L.). Results show that trout with higher testosterone levels prior to spawning have higher levels of oxidative damage at the time that they spawn (although by the time of spawning testosterone levels had dropped, leading to a negative relationship between testosterone and oxidative damage at that time). Cortisol levels were not directly related to oxidative damage or antioxidant capacity, but concentrations of this hormone were positively related to levels of fungal infection, which was itself associated both with lower antioxidant capacity and lower levels of oxidative damage. These results highlight the complexity of interactions between different components of the endocrine system and metabolism and suggest that caution be used in interpreting relationships between a single hormone and indicators of oxidative balance or other fitness proxies.     

Apolipoprotein E deficiency promotes increased oxidative stress and compensatory increases in antioxidants in brain tissue

The epsilon 4 allele of the apolipoprotein E gene (ApoE) is associated with Alzheimer's disease (AD). The extent of oxidative damage in AD brains correlates with the presence of the E4 allele of ApoE, suggesting an association between the ApoE4 genotype and oxygen-mediated damage in AD. We tested this hypothesis by subjecting normal and transgenic mice lacking ApoE to oxidative stress by folate deprivation and/or excess dietary iron. Brain tissue of ApoE-deficient mice displayed increased glutathione and antioxidant levels, consistent with attempts to compensate for the lack of ApoE. Folate deprivation and iron challenge individually increased glutathione and antioxidant levels in both normal and ApoE-deficient brain tissue. However, combined treatment with folate deprivation and dietary iron depleted antioxidant capacity and induced oxidative damage in ApoE-deficient brains despite increased glutathione, indicating an inability to compensate for the lack of ApoE under these conditions. These data support the hypothesis that ApoE deficiency is associated with oxidative damage, and demonstrate a combinatorial influence of genetic predisposition, dietary deficiency, and oxidative stress on oxidative damage relevant to AD.     

Effect of overexpression of Bcl-2 on cellular oxidative damage, nitric oxide production, antioxidant defenses, and the proteasome

Bcl-2 is a gene family involved in the suppression of apoptosis in response to a wide range of cellular insults. Multiple papers have suggested a link between Bcl-2 and oxidative damage/antioxidant protection. We therefore examined parameters of antioxidant defense and oxidative damage in two different cell lines, NT-2/D1 (NT-2) and SK-N-MC, overexpressing Bcl-2 as compared with vector-only controls. Bcl-2 transfectants of both cell lines were more resistant to H₂O₂ and showed increases in GSH level and Cu/Zn-superoxide dismutase (SOD1) activity, but not in Mn-superoxide dismutase, glutathione peroxidase, or glutathione reductase activities. Catalase activity was increased in SK-N-MC cells. Overexpression of Bcl-2 did not significantly decrease levels of oxidative DNA damage (measured as 8-hydroxyguanine) or lipid peroxidation, but it decreased levels of 3-nitrotyrosine in both cell lines and protein carbonyls in SK-N-MC cells only. It also increased proteasome activity in both cell lines. We conclude that Bcl-2 raises cellular antioxidant defense status, but this is not necessarily reflected in decreased levels of oxidative damage to DNA and lipids. The ability of Bcl-2 overexpression to decrease 3-nitrotyrosine levels suggests that it may decrease formation of peroxynitrite or other reactive nitrogen species; this was confirmed as decreased production of NO₂⁻/NO₃⁻ in the transfected cells and a fall in the level of nNOS protein.     

Eryptosis and oxidative damage in type 2 diabetic mellitus patients with chronic kidney disease

It has been suggested that oxidative stress may participate in the progression of diabetes and its complications. Long-term complications of type 2 diabetes mellitus (T2DM) include retinopathy, atherosclerosis, shortened life span of erythrocytes, nephropathy, and chronic kidney disease (CKD). Oxidative damage has been associated with erythrocyte apoptosis induction in other pathological conditions. Our aim was to study the presence of eryptosis and its possible relationship with oxidative damage in patients with T2DM without CKD (T2DM/CKD(-)) and in patients with T2DM and CKD (T2DM/CKD(+)).Oxidative damage of lipids erythrocytes were increased in diabetic patients. The highest lipoperoxidation was found in T2DM/CKD(+). Likewise, the lower plasma total antioxidant capacity, GSH/GSSG ratio, and GSH in erythrocytes were found in T2DM/CKD(+) patients. A negative correlation was found between plasma total antioxidant capacity and oxidative damage. Phosphatidylserine (PS) externalization was measured in erythrocytes to evaluate eryptosis. Annexin binding in erythrocytes of T2DM/CKD(+) patients was higher than in healthy subjects and T2DM/CKD(-) patients. A positive correlation between lipoperoxidation and PS externalization in erythrocytes was found. This work showed that the erythrocytes of diabetic patients have increased oxidative damage, a reduction of antioxidant systems and more erythrocyte PS externalization. The duration of diabetes and the presence of CKD increase both oxidative damage and eryptosis. It is possible that a longer time of evolution induces an increase in erythrocyte oxidative damage and the consumption of blood antioxidant systems, adding to the osmotic stress in CKD and so contributes to an increase in PS externalization in diabetic patients.     

Effects of Chronic Haloperidol and/or Clozapine on Oxidative Stress Parameters in Rat Brain

Decreased antioxidant activity is considered as one of the causes of tardive dyskinesia in schizophrenic patients in a prolonged neuroleptic treatment course. Haloperidol (HAL) has been hypothesized to increase oxidative stress, while clozapine (CLO) would produce less oxidative damage. The objective was to determine whether CLO for 28 days could reverse or attenuate HAL-induced oxidative damage in animals previously treated with HAL for 28 days. HAL significantly increased thiobarbituric acid reactive substances levels in the cortex (CX) and striatum and increased protein carbonyls in hippocampus (HP) and CX and this was not attenuated by CLO treatment. In the total radical trapping antioxidant parameter assay there was a decrease in the HP total antioxidant potential induced by HAL and by treatment with HAL + CLO. Our findings demonstrated that the atypical antipsychotic CLO could not revert oxidative damage caused by HAL.     

Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging?

The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is life span, i.e., does altering oxidative stress/damage change life span? Mice with genetic manipulations in their antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in life span. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory: increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean that (a) oxidative stress plays a very limited, if any, role in aging but a major role in health span and/or (b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an “antiaging” action, leading to changes in life span, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging.     

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.     

Commentary Oxidative Stress, Nutrition and Health. Experimental Strategies for Optimization of Nutritional Antioxidant Intake in Humans

Reactive oxygen species and reactive nitrogen species are formed in the human body. Endogenous antioxidant defences are inadequate to scavenge them completely, so that ongoing oxidative damage to DNA, lipids, proteins and other molecules can be demonstrated and may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. Hence diet-derived antioxidants may be particularly important in protecting against these diseases. Some antioxidants (e.g. ascorbate, certain flavonoids) can exert pro-oxidant actions in vitro, often by interaction with transition metal ions. The physiological relevance of these effects is uncertain, as is the optimal intake of most diet-derived antioxidants. In principle, these questions could be addressed by examining the effects of dietary composition and/or antioxidant supplementation upon parameters of oxidative damage in vivo. The methods available for measuring steady-state damage (i.e. the balance between damage and repair or replacement of damaged molecules) and the actual rate of damage to DNA, proteins and lipids are reviewed, highlighting areas in which further methodological development is urgently required.     

Damage to liposomal lipids: protection by antioxidants and cholesterol-mediated dehydration

Liposomes composed of egg phosphatidylcholine (EPC) (13.4%, of the acyl chains being polyunsaturated fatty acids (PUFA)) and EPC/cholesterol (10:1 mol/mol) were studied for factors that affect liposomal lipid oxidative damage and hydrolysis upon long-term (16 months) storage. Factors studied include: (1) levels of lipid/water interface hydration, related to the presence of cholesterol in the lipid bilayer; (2) the membrane-associated antioxidant vitamin E; (3) the water-soluble antioxidant Tempol; and (4) exposure to light. Liposomal dispersions were stored at room temperature, either exposed to or protected from daylight, for a period of 16 months. Chemical and physical changes were monitored at several time points to assess oxidative and hydrolytic degradation of liposomal lipids. The conclusions of the study are: (1) PUFA are the most sensitive component of the liposome bilayer to oxidative degradation damage during long-term storage; (2) EPC liposomes are more sensitive to degradation during storage than EPC cholesterol liposomes, the presence of cholesterol in the lipid bilayer having a protective effect, probably due to its effect in decreasing the lipid-bilayer hydration; (3) oxidative degradation is the major process during long-term storage, having an earlier onset than the hydrolytic degradation: and (4) Tempol provided significantly better protection than vitamin E to EPC liposomal PUFA against oxidative damage during long-term storage. The relevance of cholesterol's presence, as a 'drying agent', in membranes containing PUFA to resistance of biological membranes to oxidative damage is discussed.     

Antioxidant effects of dehydroepiandrosterone and 7alpha-hydroxy-dehydroepiandrosterone in the rat colon, intestine and liver

This study examined in healthy male Wistar rats the in vivo antioxidant effect of dehydroepiandrosterone (DHEA) and 7alpha-hydroxy-DHEA administered by intraperitoneal injections (50 mg/kg body weight) for 2 or 7 days. Markers of oxidative damage to lipids (thiobarbituric acid-reacting substances, TBARS) and to proteins (protein carbonyls) were assessed in colon, small intestine, and liver homogenates. DHEA and 7alpha-hydroxy-DHEA caused a decrease in body weight. DHEA treatment significantly increased liver, colon, and small intestine cell weights. After 7 days, DHEA exerted an antioxidant effect in all organs studied. In the colon, oxidative damage protection was accompanied by a goblet cell proliferation and increase in acidic mucus production. After 2 days, the antioxidant effect of 7alpha-hydroxy-DHEA was mainly observed in the liver. Nonprotein sulfhydryl groups (mostly glutathione levels) were altered by DHEA in the liver whereas they remained unchanged after 7alpha-hydroxy-DHEA treatment. The results indicate that in healthy animals, DHEA exerts a protective effect, particularly in the colon, by reducing the tissue susceptibility to oxidation of both lipids and proteins. This effect was not limited to a specific tissue, whereas the metabolite 7alpha-hydroxy-DHEA exerted its antioxidant effect towards the two markers of oxidative damage earlier than DHEA, and mainly in the liver.     

Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid

We have previously demonstrated that acute hyperhomocysteinemia induces oxidative stress in rat brain. In the present study, we initially investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative damage, namely total radical-trapping antioxidant potential and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), as well as on DNA damage in parietal cortex and blood of rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of Hcy (0.3-0.6 micromol/g body weight), and/or folic acid (0.011 micromol/g body weight) from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, parietal cortex and total blood was collected. Results showed that chronic homocysteine administration increased DNA damage, evaluated by comet assay, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in parietal cortex and blood/plasma. Folic acid concurrent administration prevented homocysteine effects, possibly by its antioxidant and DNA stability maintenance properties. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in disorders that accumulate homocysteine.     

Oxidative stress,circulating antioxidants,and dietary preferences in songbirds

Oxidative stress is an unavoidable consequence of metabolism and increases during intensive exercise. This is especially problematic for migratory birds that metabolize fat to fuel long-distance flight. Birds can mitigate damage by increasing endogenous antioxidants (e.g. uric acid) or by consuming dietary antioxidants (e.g. tocopherol). During flight, birds may increase protein catabolism of lean tissue which may increase circulating uric acid and many birds also consume an antioxidant-rich frugivorous diet during autumn migration. We evaluated three related hypotheses in a migratory passerine: (1) protein consumption is positively related to circulating antioxidants, (2) a dietary oxidative stressor [i.e. polyunsaturated fatty acid (PUFA)] influences antioxidant capacity and oxidative damage, and (3) oxidative stress influences dietary antioxidant preferences. White-throated Sparrows (Zonotrichia albicollis) consuming a high protein diet increased circulating uric acid; however, uric acid, antioxidant capacity, and oxidative stress did not differ between birds consuming a high PUFA versus a low PUFA diet, despite increased oxidative damage in high PUFA birds. Birds did not prefer antioxidant-rich diets even when fed high PUFA, low protein. We conclude that White-throated Sparrows successfully mitigated oxidative damage associated with a high PUFA diet and mounted an endogenous antioxidant response independent of uric acid, other circulating antioxidants, and dietary antioxidants.     

A comprehensive study of oxidative stress and antioxidant status in preeclampsia and normal pregnancy

Oxidative stress has been increasingly postulated as a major contributor to endothelial dysfunction in preeclampsia (PE), although evidence supporting this hypothesis remains inconsistent. This study aimed to analyze in depth the potential role of oxidative stress as a mechanism underlying endothelial damage in PE and the pregnant woman's susceptibility to the disease. To this end, indicative markers of lipoperoxidation and protein oxidation and changes in antioxidant defense systems were measured in blood samples from 53 women with PE and 30 healthy pregnant controls. Results, analyzed in relation to disease severity, showed PE women, compared with women with normal pregnancy, to have: (1) significantly enhanced antioxidant enzyme SOD and GPx activities in erythrocytes; (2) similar plasma alpha-tocopherol levels and significantly increased alpha-tocopherol/lipids in both mild and severe PE; (3) significantly decreased plasma vitamin C and protein thiol levels; (4) similar erythrocyte glutathione content, total plasma antioxidant capacity, and whole plasma oxidizability values; (5) significantly elevated plasma total lipid hydroperoxides, the major initial reaction products of lipid peroxidation, in severe PE; (6) no intracellular or extracellular increases in any of the secondary end-products of lipid peroxidation, malondialdehyde or lipoperoxides; (7) similar oxidative damage to proteins quantified by plasma carbonyl levels, immunoblot analysis, and advanced oxidation protein products assessment; and (8) significantly elevated and severity-related soluble vascular cell adhesion molecule-1 serum levels reflecting endothelial dysfunction. No correlations were found among plasma levels of circulating adhesion molecules with regard to lipid and protein oxidation markers. Globally, these data reflect mild oxidative stress in blood of preeclamptic women, as oxidative processes seem to be counteracted by the physiologic activation of antioxidant enzymes and by the high plasma vitamin E levels that would prevent further oxidative damage. These results do not permit us to conclude that oxidative stress might be a pathogenetically relevant process causally contributing to the disease.     

Oxidative DNA damage and plasma antioxidant capacity in type 2 diabetic patients with good and poor glycaemic control

Diabetes mellitus is a complex metabolic disorder characterized by a disturbance in glucose metabolism. Recent evidence suggests that increased oxidative damage as well as reduction in antioxidant capacity could be related to the complications in patients with type 2 diabetes. The aim of this study was to measure plasma antioxidant status in type 2 diabetic patients with good and poor glycaemic control and its relationship with oxidative DNA damage. Thirty-nine type 2 diabetic patients and eighteen healthy subjects were recruited for this study. We found that diabetic patients had slightly, but not significantly lower antioxidant capacity, measured with the "ferric reducing ability of plasma" (FRAP) assay, than healthy subjects. On the contrary, oxidative DNA damage (measured by the Comet assay) in leukocytes obtained from diabetic patients was significantly higher compared to healthy subjects. Taking into account glucose control, we found that the FRAP level was significantly (p<0.05) lower in diabetic subjects with poor glycaemic control than healthy subjects, while patients with good glycaemic control had FRAP values similar to controls. We also observed an unexpected positive correlation between FRAP values and oxidative DNA damage in diabetic patients; moreover, a positive correlation was found between FRAP and glucose level or HbA(1c) in patients with poor glycaemic control. In conclusion, our results confirm that patients with type 2 diabetes have a higher oxidative DNA damage than healthy subjects and that plasma antioxidant capacity is significantly lower only in patients with poor glycaemic control, moreover, in these patients FRAP values are positively correlated with glycaemic levels and HbA(1c). These observations indicate that a compensatory increase of the antioxidant status is induced as a response to free radical overproduction in type 2 diabetes. Therefore, the addition of antioxidant supplements to the current pharmacological treatment could have potentially beneficial effects in diabetic patients with poor glycaemic control.     

Black tea extract supplementation decreases oxidative damage in Jurkat T cells

The purpose of this study was to investigate the protective effect of black tea (BT) extract against induced oxidative damage in Jurkat T-cell line. Cells supplemented with 10 or 25 mg/L BT were subjected to oxidation with ferrous ions. Malondialdehyde (MDA) production as marker of lipid peroxidation, DNA single strand breaks as marker of DNA damage, and modification of the antioxidant enzyme activity, glutathione peroxidase (GPX) were measured. Results show the efficacy of BT polyphenols to decrease DNA oxidative damage and to affect GPX activity (P<0.05), while no effect was shown on MDA production. The succeeding investigation of the activity of caffeine and epigallocatechin gallate demonstrated their antioxidant potential with respect to the cellular markers evaluated. In conclusion, this study supports the protective effect of BT against ferrous ions induced oxidative damage to DNA and the ability of BT to affect the enzyme antioxidant system of Jurkat cells.     

Oxidative stress and antioxidant capacity of a terrestrially hibernating hatchling turtle

Hatchlings of the painted turtle, Chrysemys picta, hibernate terrestrially and can survive subfreezing temperatures by supercooling or by tolerating the freezing of their tissues. Whether supercooled or frozen, an ischemic hypoxia develops because tissue perfusion is limited by low temperature and/or freezing. Oxidative stress can occur if hatchlings lack sufficient antioxidant defenses to minimize or prevent damage by reactive oxygen species. We examined the antioxidant capacity and indices of oxidative damage in hatchling C. picta following survivable, 48 h bouts of supercooling (−6°C), freezing (−2.5°C), or hypoxia (4°C). Samples of plasma, brain, and liver were collected after a 24 h period of recovery (4°C) and assayed for Trolox-equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), and carbonyl proteins. Antioxidant capacity did not vary among treatments in any of the tissues studied. We found a significant increase in TBARS in plasma, but not in the brain or liver, of frozen/thawed hatchlings as compared to untreated controls. No changes were found in the concentration of TBARS or carbonyl proteins in supercooled or hypoxia-exposed hatchlings. Our results suggest that hatchling C. picta have a well-developed antioxidant defense system that minimizes oxidative damage during hibernation.     

Time Course of Peripheral Oxidative Stress as Consequence of Global Ischaemic Brain Injury in Rats

Free radicals play an important role in the pathogenesis of brain injury. This study evaluates the potential relationship between ischaemia/reperfusion (I/R)-induced brain injury, peripheral oxidative stress (lymphocyte DNA damage), plasma antioxidant potential and uric acid levels. We observed that 15 min of ischaemia were sufficient to significantly increase lymphocyte DNA damage that remained elevated at the end of early (3 h) reperfusion and at later (72 h) reperfusion time; this parameter was not significantly increased, when compared to preoperated levels. In parallel, antioxidant potential was elevated after 15 min of ischaemia, remained high at early (3 h) reperfusion and decreased again with longer (72 h) reperfusion. A close association between the plasma antioxidant status and the uric acid content has been confirmed by findings that changes in TRAP values positively correlate with uric acid concentration in rat plasma after ischaemic injury. Moreover, results of in vitro experiments with extra uric acid addition to control plasma have shown that uric acid contributes to a greater part of TRAP values. These results indicate a similar time course of brain I/R-associated oxidative stress and peripheral antioxidant defence status and/or oxidative stress in animal experiments.     

Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants

Abstract

The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants.     

A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners

This study investigated whether a 21.1 km (half-marathon) or a 42.195 km (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km and 41.195 km, respectively, were assessed 10 days before and immediately after the finish. There was no increase in the levels of endogenous DNA strand breaks immediately after half-marathon or marathon races. A statistically significant increase in the levels of oxidative DNA damage in lymphocytes was found using endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was significantly decreased after both races. The levels of plasma antioxidants such as alpha-tocopherol, beta-carotene and lycopene were close to, or higher than, those considered optimal for reducing the risk of cardiovascular diseases and there were no significant changes after the races in antioxidant capacity of LDL (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and percentage of granulocytes and monocytes able to generate oxidative burst were significantly increased after both races, but the lytic activity of NK cells was significantly increased at the end of the half-marathon; no effect was observed in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the antioxidant capacity to protect lymphocytes against DNA strand breaks and increased the formation of reactive species by phagocytes in well-nourished hobby runners indicating moderate oxidative damage during such high-intensity exercise.