Higher Glutathione Peroxidase Activity Research Articles

Peculiarities of the antioxidant status of the thyroid gland

The intensity of lipid peroxidation and activity of the antioxidant system in the thyroid gland were compared with those in the liver, kidney, heart, and frontal lobes of the cerebral hemispheres in euthyroid male Wistar rats. The thyroid gland was characterized by low activity of first-line antioxidant enzymes superoxide dismutase and catalase, considerable concentration of reduced glutathione, and high activity of glutathione peroxidase and glutathione reductase. Our results suggest that the system of glutathione metabolism determines antioxidant status of the thyroid gland.

Reinvestigation of a Selenopeptide with Purportedly High Glutathione Peroxidase Activity

A 15-amino acid long selenopeptide (15SeP) was recently reported to possess nearly the same catalytic activity as glutathione peroxidase (Gpx) for the reduction of hydrogen peroxide by glutathione (Sun, Y., Li, T. Y., Chen, H., Zhang, K., Zheng, K. Y., Mu, Y., Yan, G. L., Li, W., Shen, J. C., and Luo, G. M. (2004) J. Biol. Chem. 279, 37235-37240). Such a finding is startling considering the high efficiency of the natural enzyme and the modest catalytic properties of most short peptides. As 15SeP had been subjected only to limited chemical characterization, we prepared it by a new route involving selenocysteine-mediated native chemical ligation. High resolution matrix-assisted laser desorption ionization mass spectrometry confirmed the identity of the reaction product, whereas circular dichroism spectroscopy showed that 15SeP assumes a random coil conformation in solution. Although low levels of peroxidase activity were detectable under standard assay conditions, the peptide is >5 orders of magnitude less active than native Gpx. Our observations are incompatible with claims ascribing remarkable catalytic properties to 15SeP and suggest that the efficiency of Gpx derives from its well defined three-dimensional structure.

Differential Expression and Oxidation of MKP-1 Modulates TNF-α Gene Expression

Monocytic cells are integral in the pathogenesis of inflammatory disorders. We have shown previously that asbestos-induced p38 mitogen-activated protein (MAP) kinase activation and TNF-alpha expression are mediated by H(2)O(2) in blood monocytes. Due to the high expression and activity of catalase and glutathione peroxidase, normal alveolar macrophages do not respond in a manner similar to that of blood monocytes. Since kinase activity is tightly regulated by phosphatases, we hypothesized that the dual specificity phosphatase MAP kinase phosphatase (MKP)-1 regulates p38 activity and TNF-alpha production in alveolar macrophages due to insufficient H(2)O(2) generation in response to asbestos. We found that MKP-1 was highly expressed in alveolar macrophages, while blood monocytes had minimal expression. Inhibition of expression and activity of MKP-1 or overexpression of a catalytic mutant MKP-1 recovered p38 activity in alveolar macrophages. We questioned whether MKP-1 oxidation played a role dictating the contrasting responses of these cells to asbestos exposure, and found that overexpressed wild-type MKP-1 in monocytes was oxidized, while the mutant MKP-1 remained in the reduced form. Monocytes overexpressing either catalase or wild-type MKP-1 had decreased p38 activation and TNF-alpha production, respectively. In addition, TNF-alpha gene expression was regained in alveolar macrophages overexpressing the catalytic mutant MKP-1. These data suggest that MKP-1, through increased expression and lack of oxidation, modulates the inflammatory response in alveolar macrophages exposed to asbestos.

Synthesis, Characterization, and Antioxidant Activity of Some Ebselen Analogues

Simple synthetic routes for several analogues of the anti-inflammatory organoselenium drug, ebselen, are described. The compounds are characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques and, in some cases, by single-crystal X-ray diffraction studies. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2), tBuOOH, and Cum-OOH as substrates, and thiophenol (PhSH, 4-Me-C(6)H(4)SH) and glutathione (GSH) as cosubstrates. Density functional theory (DFT) calculations have been performed on these systems to understand the effects of various substituents on the (77)Se NMR chemical shifts; these results have been compared with the experimental data. The experimental and theoretical results suggest that the presence of a phenyl substituent on the nitrogen atom is important for the antioxidant activity of ebselen. While ebselen and its analogues are poor catalysts in aromatic thiol assays, these compounds exhibit high GPx activity when GSH is used as the cosubstrate. The poor catalytic activity of ebselen analogues in the presence of aromatic thiols such as PhSH and 4-Me-C(6)H(4)SH can be ascribed to the undesired thiol exchange reaction that takes place at the selenium center due to SeO nonbonding interactions. To understand the effects of different peroxides on the catalytic activities, we have determined the initial rates at various concentrations of GSH and peroxides. These data suggest that the nature of peroxide has little effect on the catalytic efficiencies, although the initial reaction rates observed with hydrogen peroxide were found to be higher than that with tBuOOH and Cum-OOH. In contrast to the effect of peroxides, the nature of thiols appears to have a dramatic effect on the catalytic activity of ebselen and its related derivatives.

Higher Glutathione Peroxidase Expression in Thoracic Aorta as a Protective Factor against Oxidative Stress and Atherosclerosis in Rabbits

Atherosclerosis develops in different locations of the vasculature with different degree, which may result from different antioxidant/prooxidant status. This study investigated the effect of high-fat, high-cholesterol chows, with or without vitamin E supplement (450 mg/kg diet), on lipid peroxide levels, glutathione peroxidase expression, and atheroma formation in ascending aorta, pulmonary arteries and thoracic aorta.Sixty-four rabbits were divided to be fed with 4 different chows for 6 weeks. The percentage of atherosclerosis was measured. Plasma and vascular glutathione peroxidase activity and mRNA expression, and lipid peroxide levels were also assayed.Rabbits on high-fat, high-cholesterol chows had higher lipid peroxide levels and more atherosclerosis in ascending aorta and pulmonary arteries. Tissues in thoracic aorta had higher glutathione peroxidase activity and mRNA expression without any significant increase in lipid peroxide levels and atherosclerosis. Vitamin E supplement decreased plasma lipid peroxide levels, but not in tissues, and thus could not prevent atherosclerosis.Higher glutathione peroxidase expression in the thoracic aorta inhibits oxidative stress enhancement and atheroma progression induced by high-fat, high-cholesterol chows. Vitamin E supplement at the current dosage and duration could not prevent atheroma formation.

Differences in activities of antioxidant superoxide dismutase, glutathione peroxidase and prooxidant xanthine oxidoreductase/xanthine oxidase in the normal corneal epithelium of various mammals

Under normal conditions, antioxidants at the corneal surface are balanced with the production of reactive oxygen species without any toxic effects. Danger from oxidative stress appears when natural antioxidants are overwhelmed leading to antioxidant/prooxidant imbalance. The aim of the present study was to examine the activities of enzymes contributing to the antioxidant/prooxidant balance in normal corneal epithelium of various mammals. The enzyme activities of antioxidant superoxide dismutase and glutathione peroxidase, as well as prooxidant xanthine oxidoreductase/xanthine oxidase were examined using biochemical methods. Results show that superoxide dismutase activity is high in rabbits and guinea pigs, whereas in pigs the activity is low and in cows it is nearly absent. In contrast, glutathione peroxidase activity is high in cows, pigs and rabbits, whereas in guinea pigs the activity is low. As far as prooxidant enzymes are concerned, elevated xanthine oxidoreductase/xanthine oxidase activities were found in rabbits, lower activities in guinea pigs, very low activity in cows and no activity in pigs. In conclusion, the above results demonstrate inter-species variations in activities of enzymes participating in antioxidant/prooxidant balance in the corneal epithelium. It is suggested that the levels of antioxidant and prooxidant enzymes studied in the corneal epithelium might be associated with the diurnal or nocturnal activity of animals. UV rays decompose hydrogen peroxide to damaging hydroxyl radicals and perhaps for this reason large animals with diurnal activity (cow, pig) require more effective peroxide removal (high glutathione peroxidase activity) together with the suppression of peroxide production (low superoxide dismutase activity, low xanthine oxidoreductase activity).

Selenium-Mediated Micellar Catalyst: An Efficient Enzyme Model for Glutathione Peroxidase-like Catalysis

Mimicking the properties of the selenoenzyme glutathione peroxidase (GPx) has inspired great interest. In this report, a selenium-containing micellar catalyst was successfully constructed by the self-assembly of the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) with benzeneseleninic acid (PhSeO2H) through hydrophobic and electrostatic interaction in water. The selenium-containing micellar catalyst demonstrated substrate specificity for both 3-carboxy-4-nitrobenzenethiol (ArSH, 2) and cumene hydroperoxide (CUOOH), and their complexation was confirmed by UV and fluorescence spectra. More importantly, it demonstrated high GPx activity in two assay systems. It is about 126 times more effective than the well-known GPx mimic ebselen in the classical coupled reductase assay system; however, by using hydrophobic substrate ArSH (2) as an alternative of glutathione (GSH, 1), the micellar catalyst exhibited remarkable 500-fold and 94 500-fold rate enhancements compared with that of PhSeO2H and PhSeSePh.

Tellurium‐Based Polymeric Surfactants as a Novel Seleno‐Enzyme Model with High Activity

AbstractSummary: A tellurium‐based polymeric sufactant as a seleno‐enzyme model has been constructed by employing 11‐acryloyloxyundecyltriethylammonium bromide (AUTEAB, 4) and a tellurium‐containing compound (1). It demonstrates strong substrate binding ability for thiols and high glutathione peroxidase (GPx) activity about 6 orders of magnitude more efficient than the well‐known GPx mimic PhSeSePh in an ArSH assay system. More importantly, a series of tellurium‐based polymeric micelle catalysts with the catalytic tellurium center located at various positions in the micelle have been constructed, and the dramatic difference in activity indicates that the exact match of the catalytic center and binding site plays a key role in enzyme catalytic efficiency.Schematic representation of the proposed mode of the telluro‐micelle catalysts.magnified imageSchematic representation of the proposed mode of the telluro‐micelle catalysts.

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through reactive oxygen species (ROS) and ROS-driven oxidative stress, the role of antioxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the antioxidant response of the lung correlated well with that of red blood cells (RBC). We then proceeded to test whether differences of RBC antioxidant response would predict the pneumonitis development in patients. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in 15 eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the antioxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs 6.8 units/mg for median SOD, 16.5 vs 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pretreatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

2458: High Superoxide Dismutase (SOD) and Low Glutathione Peroxidase (GPX) Activities in Red Blood Cells (RBCs) Predict Susceptibility of Lung Cancer Patients to Radiation Pneumonitis

2458: High Superoxide Dismutase (SOD) and Low Glutathione Peroxidase (GPX) Activities in Red Blood Cells (RBCs) Predict Susceptibility of Lung Cancer Patients to Radiation Pneumonitis

Renal function of chloralkali workers after the cessation of exposure to mercury vapor

The aims of the study were to assess renal function in chloralkali workers previously exposed to mercury vapor and to assess the impact of selenium status on the biomarkers of kidney function. Forty-nine chloralkali workers previously exposed to mercury vapor were compared with 49 age-matched referents in a cross-sectional study. Selected biomarkers of kidney function and biomarkers of selenium status were measured. The index group had been exposed for 13.1 (range 2.8-34.5) years on the average at a mean urinary mercury excretion of 9.3 (range 4.0-25.4) nmol/mmol creatinine a year. The exposure had ceased on an average of 4.8 (range 4.2-10.0) years prior to the examinations. No statistically significant differences were found between the groups for the measured biomarkers of kidney function. The serum selenium concentration and serum glutathione peroxidase activity were associated with the activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG). The results indicate that having higher glutathione peroxidase activity or a higher serum selenium concentration results in a lower excretion of U-NAG. This effect was the most pronounced in the oldest third of the participants. Apparently the well-known association between U-NAG and age could only be found for the participants with a lower selenium status. Increased activities of U-NAG during ongoing exposure to mercury vapor appear to be reversible upon cessation of exposure. Selenium status has a substantial impact on U-NAG activity and should be considered in studies of U-NAG excretion.

Single Chain Antibody Displays Glutathione S-Transferase Activity

Substrate binding and the subsequent reaction are the two principal phenomena that underlie the activity of enzymes, and many enzyme-like catalysts were generated based on the phenomena. The single chain variable region fragment of antibody 2F3 (scFv2F3) was elicited against hapten GSH-S-DN2phBu, a conjugate of glutathione (GSH), butyl alcohol, and 1-chloro-2,4-dinitrobenzene (CDNB); it can therefore bind both GSH and CDNB, the substrates of native glutathione S-transferases (GSTs). It was shown previously that there is a serine residue that is the catalytic group of GST in the CDR regions of scFv2F3 close to the sulfhydryl of GSH. Thus, we anticipated that scFv2F3 will display GST activity. The experimental results showed that scFv2F3 indeed displayed GST activity that is equivalent to the rat-class GST T-2-2 and exhibited pH- and temperature-dependent catalytic activity. Steady-state kinetic studies showed that the Km values for the substrates are close to those of native GSTs, indicating that scFv2F3 has strong affinities for the substrates. Compared with some other GSTs, its kcat value was found to be low, which could be caused by the similarity between the GSH-S-DN2phBu and the reaction product of GSH and CDNB. These results showed that our approach to imitating enzymes is correct, which is that an active site may catalyze a chemical reaction when a catalytic group locates beside a substrate-binding site of a receptor. It is important to consider product inhibition in hapten design in order to obtain a mimic with a high catalytic efficiency.

Selenium, an Ambivalent Factor in Diabetes? Established Facts, Recent Findings and Perspectives

It is widely known that selenium develops its biological activity via an active selenocysteine residue in the catalytically active centre of functional selenoproteins. By its function in glutathione peroxidases and thioredoxin reductases selenium contributes to a remarkable extent to the maintenance of the cellular antioxidative balance when taken up at the recommended dietary level (animals: 0.1 - 0.3 μg/kg diet, humans: 50 - 150 µg Se daily). In recent years an interesting physiological aspect has been found for selenate (selenium oxidation state +VI). High doses of selenate displayed antidiabetic properties when applied to diabetic animals or added to the media of tissue cultures. Thus selenate treatment could be shown to normalise hyperglycaemia as well as changed activities of glycolytic and gluconeogenic marker enzymes. Mechanistically an increased phosphorylation of single proteins of the insulin signalling cascade could be attributed to the insulinomimetic action of selenate. The examination of the antidiabetic features of selenate in type II diabetic animals revealed that the increase in phosphorylation is presumably based on the inhibition of protein tyrosine phosphatases, which act as negative regulators of insulin signalling. In contrast to the antidiabetic features of high selenate doses, selenite administration to diabetic animals showed no effect on diabetes. In a recent study it could even be demonstrated that the overexpression of glutathione peroxidase 1 (the best characterized selenoprotein) in healthy mice led to an increase in insulin resistance and obesity. These results could partially be confirmed by the data of our most recent investigation in which a high expression and activity of glutathione peroxidase, obtained by feeding selenium at the nutritionally recommended level and at a moderately supranutritive level corresponded to an up-regulated expression of proteins whose expression is increased in insulin resistant type 2 diabetes. From studies on the role of selenium in diabetes carried out so far it can be concluded that selenium plays an ambivalent role with regard to diabetes depending on the compound and on the applied concentration. Thus only high doses of selenate evolve antidiabetic properties. Investigations into an even negative influence of moderate supranutritive doses of selenium on diabetes and the molecular events linked to this are necessary. The review summarizes the information currently available on the ambivalent role of selenium in diabetes which seems to depend on the chemical form and the applied concentration. Established facts, recent findings of our own studies using microarray analysis and RT-PCR and perspectives of the role of selenium in diabetes are presented and discussed against the background of selenium metabolism. Keywords: Selenium, selenate, selenite, antidiabetic effects and insulin resistance

Both the NADPH oxidase and the mitochondrial respiratory chain regulate chemokine gene expression.

Alveolar macrophages are involved in the pathogenesis of immune and inflammatory disorders of the lung. One hallmark of the cellular response to inflammation is the recruitment of neutrophils to sites of inflammation. The generation of chemotactic proteins, such as MIP-2, triggers neutrophil recruitment. We have previously shown that alveolar macrophages spontaneously generate high levels of ROS, especially O2.−-, and their high catalase and glutathione peroxidase activity limits the effectiveness of H2O2 to act as a signaling mediator. In this study, we ask if O2.− generation in alveolar macrophages had a role in the expression of inflammatory genes. Specifically, we hypothesized that O2.− generation is necessary for MIP-2 gene expression in alveolar macrophages after TNF-α stimulation. We found that TNF-α increased O2.− generation by activating both NADPH oxidase and the mitochondrial respiratory chain in alveolar macrophages. TNF-α-induced O2.− generation was necessary for MIP-2 gene expression because inhibition of NADPH oxidase, the mitochondrial respiratory chain, or over expression of SOD significantly inhibited expression of MIP-2. In addition, TNF-α-induced NADPH oxidase and mitochondrial respiratory chain activity were necessary for ERK MAP kinase activation, and ERK activity was essential for MIP-2 gene expression. Furthermore, over expression of a constitutive active MEK1, the upstream kinase that activates ERK, significantly increased TNF-α-induced chemokine gene expression. These results suggest that in alveolar macrophages, O2.− generation from both NADPH oxidase and the mitochondrial respiratory chain mediates MIP-2 gene expression after TNF-α stimulation in an ERK-dependent manner.

Anti-Thyroid Drugs and Thyroid Hormone Synthesis: Effect of Methimazole Derivatives on Peroxidase-Catalyzed Reactions

Syntheses and characterization of the selenium analogue (MSeI) of anti-thyroid drug methimazole and a series of organoselenium compounds bearing N-methylimidazole pharmacophore are described. In contrast to the sulfur compound that exists predominantly in its thione form, the selenium analogue exists in a selenol form, which spontaneously oxidizes in air to produce the corresponding diselenide. The reduction of the diselenide by GSH or NaBH(4) affords the biologically active selenol, which effectively inhibits the lactoperoxidase (LPO) activity in vitro. The monoselenides having N-methylimidazole moiety are found to be much less active than the selenol, suggesting that the presence of a selenol moiety is important for the LPO inhibition. The kinetic and mechanistic studies reveal that MSeI inhibits the LPO activity by reducing the H(2)O(2), providing a novel method to reversibly inhibit the enzyme. Although MSeI strongly inhibits LPO, the enzyme's activity can be completely recovered by increasing the H(2)O(2) concentration. On the other hand, the inhibition by methimazole (MMI), the sulfur analogue, cannot be reversed by increasing the H(2)O(2) concentration, leading to a complete inactivation of the enzyme. The reversible inhibition of LPO by some of the selenium derivatives is correlated with their glutathione peroxidase (GPx) activity, and the high GPx activity of the selenium compounds as compared with their sulfur analogues suggests that the selenium derivatives may protect the thyroid gland from oxidative damage.

E6* oncoprotein expression of human papillomavirus type‐16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defence

Clinical observations of non-melanoma skin cancer in immunocompromised patients, such as organ transplant recipients, suggest co-operative effects of human papillomavirus (HPV) and ultraviolet (UV) radiation. The aim of the present study is to evaluate UV sensitivity and DNA damage formation according to antioxidant status in HPV16-infected keratinocytes. We used SKv cell lines, infected with HPV16 and well characterized for their proliferative and tumorigenic capacities. We showed that SKv cell lines presented various E6* (a truncated form of E6) RNA levels. We demonstrated that the higher oncoprotein RNA expression level was associated with a higher resistance to solar-simulated radiation, more specifically to UVB radiation and to hydrogen peroxide. Moreover, this high resistance was associated with a low oxidative DNA damage formation after UV radiation and was related to high glutathione content and glutathione peroxidase activities. Therefore, the results of our study suggest that E6* levels could modulate the glutathione/glutathione peroxidase pathway providing a mechanism to protect HPV-infected keratinocytes against an environmental oxidative stress, such as UV radiation.

Higher fat and carbohydrate intake in dementia patients is associated with increased blood glutathione peroxidase activity

Mounting evidence implicates diets high in fats and processed sugars with increased generation of free radicals in animals. It is still not clearly established whether such a diet alters antioxidant balance in dementia patients, where an oxidative stress status may already exist. The disruption to lipid metabolism by oxidative stress has been recently linked to neurodegeneration and clinical disease. The aim of this study is to assess the relationship between fat, sugar, carbohydrate and caloric intake levels, and antioxidant status in patients with mild to moderate dementia. The levels of 3 essential endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase) were measured in the blood of 26 dementia subjects and 26 cognitively unimpaired controls. Concurrently, the intake levels of relevant nutrients and dietary antioxidants were assessed in all subjects. A statistically significant positive association was observed in the dementia group between glutathione peroxidase activity and the intake of fats (r = 0.44; p = 0.023), carbohydrates (r = 0.46; p = 0.018), total sugars (r = 0.51; p = 0.007) and calories (r = 0.47; p = 0.14). The only significant association in the control group was observed between glutathione peroxidase and fat (r = 0.47; p = 0.015). The higher glutathione peroxidase activity among subjects with greater intake of fats, carbohydrates and sugars may represent a compensatory response to the additional increase in oxidative stress in dementia. Our data shed light on the influence of dietary intake on the oxidant-antioxidant system in mild to moderate dementia patients.

Antioxidant effect of virgin olive oil in patients with stable coronary heart disease: a randomized, crossover, controlled, clinical trial

The Mediterranean diet, in which olive oil is the main source of fat, has been associated with a reduced incidence of coronary heart disease (CHD) and low blood pressure levels. Virgin olive oil (VOO), besides containing monounsaturated fat, is rich in phenolic compounds (PC) with antioxidant properties. The aim of this study was to examine the antioxidant and anti-hypertensive effect of two similar olive oils, but with differences in their PC (refined: 14.7 mg/kg versus virgin: 161.0 mg/kg), in 40 males with stable CHD. The study was a placebo controlled, crossover, randomized trial. A raw daily dose of 50 mL of VOO and refined olive oil (ROO) were sequentially administered over two periods of 3 weeks, preceded by 2-week washout periods in which ROO was used. Lower plasma oxidized LDL ( p < 0.001) and lipid peroxide levels ( p = 0.003), together with higher activities of glutathione peroxidase ( p = 0.033), were observed after VOO intervention. Systolic blood pressure decreased after intake of VOO ( p = 0.001) in hypertensive patients. No changes were observed in diastolic blood pressure, glucose, lipids, and antibodies against oxidized LDL. Consumption of VOO, rich in PC, could provide beneficial effects in CHD patients as an additional and complementary intervention to the pharmacological treatment.

32 Oxidative stress associated with training and competing in an ironman triathlon

The benefits of regular moderate exercise in reducing cardiovascular disease are well established. However, the effect of ultra-endurance exercise remains uncertain as aerobic exercise increases the production of reactive oxygen species (ROS). ROS produce oxidative stress and molecular damage. The present study investigated markers of oxidative stress (malondialdehyde (MDA)), antioxidant status (glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD)) and arterial stiffness; in a group of athletes training for and competing in an Ironman triathlon (3.8km swim, 180km ride, 42.2km run). Resting measures were taken between three and seven days prior to the triathlon (23 male, 6 female ultra-endurance triathletes [36.6 years]; and 29 matched controls [35.3 years] active < 180 minutes. week-l). Resting samples revealed the athletes had significantly lower MDA concentration (p<0.05) and higher activities of GPX and CAT (p<0.01 & 0.001 respectively) compared to controls. There were no differences between athletes and controls in measures of arterial stiffness or any other blood markers associated with antioxidant status. The amount of time spent exercise training was positively related to resting MDA concentration (r=0.37; p=0.05), resting SOD activity (r=0.57; p=0.001) and resting LDL concentration (r=0.38; p=0.04). Blood was again sampled within 15 minutes of finishing the race. Analysis found a significant increase in MDA concentration (p=0.03), decreases in the activities of GPX (p<0.001), CAT (p<0.001) and SOD) (p=0.001). In summary, although ultra-endurance athletes have lower oxidative stress during training, an Ironman triathlon results in a decrease in antioxidant capacity and an increase in oxidative stress.

Effect of five cysteine‐containing compounds on three lipogenic enzymes in Balb/cA mice consuming a high saturated fat diet

The in vivo effects of N-acetyl cysteine (NAC), S-allyl cysteine, S-ethyl cysteine (SEC), S-methyl cysteine (SMC), and S-propyl cysteine (SPC) against hyperlipidemia development and oxidation stress in Balb/cA mice consuming a high saturated fat diet were examined. The influence of these agents on plasma levels of glucose, insulin, uric acid, TG, cholesterol, and the activity of three lipogenic enzymes--glucose-6-phosphate dehydrogenase, malic enzyme, and FA synthase--was determined. All mice consumed the coconut oil-basd, high saturated fat diet, water, and cysteine or one of the five cysteine-containing compounds for 4 wk. The diet with 18% saturated fat significantly elevated the activity of three lipogenic enzymes and significantly increased TG and cholesterol biosynthesis in plasma and liver (P < 0.05). When compared with the water and cysteine groups, the treatments from five cysteine-containing agents significantly reduced high saturated fat diet-increased malic enzyme and FA synthase activities, and significantly lowered TG levels in plasma and liver (P< 0.05); however, only NAC, SAC, and SMC treatments significantly reduced cholesterol levels in plasma and liver (P < 0.05). The five cysteine-containing agents significantly restored high saturated fat diet-decreased glutathione peroxidase (GPX) activity in liver (P< 0.05); however, only SMC and SPC significantly restored GPX activity in heart and kidney (P< 0.05). These agents also significantly improved high saturated fat diet-related hyperglycemia, hyperuricemia, and oxidation stress (P < 0.05). These data support the hypothesis that these compounds are potential multiply-protective agents for hyperlipidemia prevention or therapy.