Exercise Training Reduces Sympathetic Modulation on Cardiovascular System and Cardiac Oxidative Stress in Spontaneously Hypertensive Rats

BACKGROUND Spontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether ET alters cardiac sympathetic modulation on cardiovascular system and whether a correlation exists between cardiac oxidative stress and hypertrophy. METHODS Male SHRs (15-weeks old) were divided into sedentary hypertensive (SHR, n = 7) and exercise-trained hypertensive rats (SHR-T, n = 7). Moderate ET was performed on a treadmill (5 days/week, 60 min, 10 weeks). After ET, cardiopulmonary reflex responses were assessed by bolus injections of 5-HT. Autoregressive spectral estimation was performed for systolic arterial pressure (SAP) with oscillatory components quantified as low (LF: 0.2-0.75 Hz) and high (HF:0.75-4.0 Hz) frequency ranges. Cardiac NE concentration, lipid peroxidation, antioxidant enzymes activities, and total nitrates/nitrites were determined. RESULTS ET reduced mean arterial pressure, SAP variability (SAP var), LIF of SAP, and cardiac hypertrophy and increased cardiopulmonary reflex responses. Cardiac lipid peroxidation was decreased in trained SHRs and positively correlated with NE concentrations (r= 0.89, P < 0.01) and heart weight/body weight ratio (r= 0.72, P < 0.01), and inversely correlated with total nitrates/nitrites (r= -0.79, P < 0.01). Moreover, in trained SHR, cardiac total nitrates/nitrites were inversely correlated with NE concentrations (r= -0.82, P < 0.01). CONCLUSIONS ET attenuates cardiac sympathetic modulation and cardiac hypertrophy, which were associated with reduced oxidative stress and increased nitric oxide (NO) bioavailability. Am J Hypertens 2008;21:1138-1193 (C) 2008 American Journal of Hypertension, Ltd.

Blood Cardioplegia with N-Acetylcysteine May Reduce Coronary Endothelial Activation and Myocardial Oxidative Stress

Objectives: The aim of this prospective study was to compare the efficacy of intermittent antegrade blood cardioplegia with or without n-acetylcysteine (NAC) in reducing myocardial oxidative stress and coronary endothelial activation. Methods: Twenty patients undergoing elective isolated coronary artery bypass graft surgery were randomly assigned to receive intermittent antegrade blood cardioplegia (32 degrees C-34 degrees C) with (NAC group) or without (control group) 300 mg of NAC. For these 2 groups we compared clinical outcome, hemodynamic evolution, systemic plasmatic levels of troponin I, and plasma concentrations of malondialdehyde (MDA) and soluble vascular adhesion molecule 1 (sVCAM-1) from coronary sinus blood samples. Results: Patient demographic characteristics and operative and postoperative data findings in both groups were similar. There was no hospital mortality. Comparing the plasma levels of MDA 10 min after the aortic cross-clamping and of sVCAM-1 30 min after the aortic cross-clamping period with the levels obtained before the aortic clamping period, we observed increases of both markers, but the increase was significant only in the control group (P=.039 and P=.064 for MDA; P=.004 and P=.064 for sVCAM- 1). In both groups there was a significant increase of the systemic serum levels of troponin I compared with the levels observed before cardiopulmonary bypass (P<.001), but the differences between the groups were not significant (P=.570). Conclusions: Our investigation showed that NAC as an additive to blood cardioplegia in patients undergoing on-pump coronary artery bypass graft surgery may reduce oxidative stress and the resultant coronary endothelial activation.

Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.

Effect of n-3 polyunsaturated fatty acids on oxidative stress in rats supplemented with different doses of fish oil

The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n-3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY-FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and ?-linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY-FISH and FISH diets reducing the n-6/n-3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY-FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P < 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY-FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n-3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY-FISH, and FISH groups, respectively. Thus, n-3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration

Behavior and viability of spontaneous oxidative stress-resistant Lactococcus lactis mutants in experimental fermented milk processing

Previously, we isolated two strains of spontaneous oxidative (SpOx2 and SpOx3) stress mutants of Lactococcus lactis subsp cremoris. Herein, we compared these mutants to a parental wild- type strain (J60011) and a commercial starter in experimental fermented milk production. Total solid contents of milk and fermentation temperature both affected the acidification profile of the spontaneous oxidative stress- resistant L. lactis mutants during fermented milk production. Fermentation times to pH 4.7 ranged from 6.40 h (J60011) to 9.36 h (SpOx2); V(max) values were inversely proportional to fermentation time. Bacterial counts increased to above 8.50 log(10) cfu/mL. The counts of viable SpOx3 mutants were higher than those of the parental wild strain in all treatments. All fermented milk products showed post-fermentation acidification after 24 h of storage at 4 degrees C; they remained stable after one week of storage.

High Glucose-Mediated Oxidative Stress Impairs Cell Migration

Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG), 25 mM D-glucose (high glucose, HG) or 25 mM L-glucose medium (osmotic control - OC), we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC). We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

Giant Vesicles under Oxidative Stress Induced by a Membrane-Anchored Photosensitizer

We have synthesized the amphiphile photosensitizer PE-porph consisting of a porphyrin bound to a lipid head-group. We studied by optical microscopy the response to light irradiation of giant unilamellar vesicles of mixtures of unsaturated phosphatidylcholine lipids and PE-porph. In this configuration, singlet oxygen is produced at the bilayer surface by the anchored porphyrin. Under irradiation, the PE-porph decorated giant unilamellar vesicles exhibit a rapid increase in surface area with concomitant morphological changes. We quantify the surface area increase of the bilayers as a function of time and photosensitizer molar fraction. We attribute this expansion to hydroperoxide formation by the reaction of the singlet oxygen with the unsaturated bonds. Considering data from numeric simulations of relative area increase per phospholipid oxidized (15%), we measure the efficiency of the oxidative reactions. We conclude that for every 270 singlet oxygen molecules produced by the layer of anchored porphyrins, one eventually reacts to generate a hydroperoxide species. Remarkably, the integrity of the membrane is preserved in the full experimental range explored here, up to a hydroperoxide content of 60%, inducing an 8% relative area expansion.

Possible Relationship Between Performance and Oxidative Stress in Endurance Horses

The purpose of this study was to evaluate oxidative stress, antioxidant biomarkers, and performance during a multiday 210-km endurance race. Nine endurance athlete horses participated in this study. Samples were always taken at the same times of day, before the beginning of the race and after every day of competition. Analytic measurements included glutathione reductase (GR) and catalase activity, thiobarbituric acid-reactive substances (TBARs), and reactive carbonylated derivatives. Competition intensity was low, with an average speed of 12.56 +/- 0.9 km/h. Four horses were unable to finish the race because of metabolic problems or fatigue. GR activity increased progressively (P < .001) throughout the competition, and TBARs showed a significant rise compared with baseline values (P < .01) but remained at the same levels throughout the 3 days of competition. Catalase and reactive carbonylated derivatives did not show any significant alterations in any time period. The best performance was obtained from horses who demonstrated higher GR capacity and/or lower TBAR concentration. In conclusion, redox. status seems to modulate horses` performance in endurance races, but further Studies are needed to better determine the adequate oxidant/antioxidant ratio to acquire optimal performance.

Oxidative stress biomarkers of exposure in the blood of cichlid species from a metal-contaminated river

The oxidative stress biomarkers of exposure, such as reduced glutathione (GSH), activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the levels of lipid peroxidation (LPO), were measured in the blood of three cichlid fish (Oreochromis niloticus, Tilapia rendalli, and Geophagus brasiliensis) taken during two seasons from two sites, unpolluted and polluted by industrial effluents, to evaluate the effectiveness of these biomarkers in assessing the impact of water contamination. The LPO levels in the blood were higher in fish from the metal-contaminated site and the chronic exposure led to significant changes in GPx, CAT, and SOD activities in all three cichlid species. The considerable variation of responses in these cichlids to water contamination evidenced differences in sensitivity to the metal contamination and/or in the potential to respond to it highlighting the importance of using a set of related biomarkers to assess the impact of water contamination. (C) 2007 Elsevier Inc. All rights reserved.

Photochemical damage and comparative performance of superoxide dismutase and ascorbate peroxidase in sugarcane leaves exposed to paraquat-induced oxidative stress

The physiological responses of sugarcane (Succharion officinarum L.) to oxidative stress induced by methyl viologen (paraquat) were examined with respect to photochemical activity, chlorophyll content, lipid peroxidation and superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities. Thirty-day-old sugarcane plants were sprayed with 0, 2, 4, 6 and 8 mM methyl viologen (MV). Chlorophyll fluorescence was measured after 18 It and biochemical analyses were performed after 24 and 48 h. Concentrations of MV above 2 mM caused significant damage to photosystem II (PSII) activity. Potential and effective quantum efficiency of PSII and apparent electron transport rate were greatly reduced or practically abolished. Both chlorophyll and soluble protein contents steadily decreased with MV concentrations above 2 mM after 24 It of exposure, which became more pronounced after 48 It, achieving a 3-fold decrease. Insoluble protein contents were little affected by MV. Oxidative stress induced by MV was evidenced by increases in lipid peroxidation. Specific activity of SOD increased, even after 48 h of exposure to the highest concentrations of MV, but total activity on a fresh weight basis did not change significantly. Nondenaturing YAGE assayed with H2O2 and KCN showed that treatment with MV did not change Cu/Zn-SOD and MnSOD isoform activities. In contrast, APX specific activity increased at 2 mM MV but then dropped at higher doses. Oxidative damage induced by MV was inversely related to APX activity. It is suggested that the major MV-induced oxidative damages in sugarcane leaves were related to excess H2O2, probably in chloroplasts, caused by an imbalance between SOD and APX activities, in which APX was a limiting step. Reduced photochemical activity allowed the early detection of the ensuing oxidative stress. (c) 2007 Elsevier Inc. All rights reserved.

EFFECT OF n-3 POLYUNSATURATED FATTY ACIDS ON OXIDATIVE STRESS IN RATS SUPPLEMENTED WITH DIFFERENT DOSES OF FISH OIL

The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n-3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY-FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and alpha-linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY-FISH and FISH diets reducing the n-6/n-3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY-FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P < 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY-FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n-3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY-FISH, and FISH groups, respectively. Thus, n-3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration. PRACTICAL APPLICATIONS Because fish oil intake is associated with risk reduction for cardiovascular disease, individuals are taking supplements containing a high dose of fish oil. However, there is no scientific consensus if the intake of a high dose of fish oil could increase the oxidative stress. Thus, more studies are necessary to assure the safety of this kind of supplementation.

Effect of n-3 fatty acids and statins on oxidative stress in statin-treated hypercholestorelemic and normocholesterolemic women

Introduction: Although the combination of statins with n-3 fatty acids seems to be beneficial under the lipid profile aspect, there is little information about the interaction of these two compounds on oxidative stress. Objective: Evaluate the interaction between statins and n-3 fatty acids on oxidative stress in women, using a 2(2) factorial design. Methods: Forty-three women participated in this crossover design. They were separated into two groups in which 20 were under statin treatment for more than 6 months, and 23 were normolipidemic. Within each group, half of the patients received capsules containing 2.4 g/day of a mixture of EPA and DHA for 6 weeks, while the other half received a mixture of soya and corn oil. After a period of 90 days of washout, the groups were switched, and received the supplementation for 6 weeks more. Results: Statins reduced serum LDL and increased SOD expression. n-3 fatty acids increased the plasma malondialdehyde and SOD activity but reduced catalase expression (p < 0.05). The interaction involving statins and n-3 fatty acids was nearly significant to the serum triacylglycerol reduction (p = 0.054). Conclusion: Combining statins and n-3 fatty acids is an excellent strategy to reduce plasma cholesterol and triacylglycerol concentration in women. However, n-3 fatty acids increased the oxidative stress and the pleiotropic effect of statins seemed to be not enough to counterbalance this result. Our data also suggested that the mechanism by which n-3 fatty acids interfere in oxidative stress can be associated with antioxidant enzymes expression and activity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Classification of individuals with dyslipidaemia controlled by statins according to plasma biomarkers of oxidative stress using cluster analysis

Oxidative stress is a physiological condition that is associated with atherosclerosis. and it can be influenced by diet. Our objective was to group fifty-seven individuals with dyslipidaemia controlled by statins according to four oxidative biomarkers, and to evaluate the diet pattern and blood biochemistry differences between these groups. Blood samples were collected and the following parameters were evaluated: diet intake; plasma fatty acids; lipoprotein concentration; glucose; oxidised LDL (oxLDL); malondialdehyde (MDA): total antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing ability power assays. Individuals were separated into five groups by cluster analysis. All groups showed a difference with respect to at least one of the four oxidative stress biomarkers. The separation of individuals in the first axis was based upon their total antioxidant activity. Clusters located on the right side showed higher total antioxidant activity, higher myristic fatty acid and lower arachidonic fatty acid proportions than clusters located on the left side. A negative correlation was observed between DPPH and the peroxidability index. The second axis showed differences in oxidation status as measured by MDA and oxLDL concentrations. Clusters located on the Upper side showed higher oxidative status and lower HDL cholesterol concentration than clusters located on the lower side. There were no differences in diet among the five clusters. Therefore, fatty acid synthesis and HDL cholesterol concentration seem to exert a more significant effect on the oxidative conditions of the individuals with dyslipidaemia controlled by statins than does their food intake.

Biomarkers of oxidative stress and endothelial dysfunction in glucose intolerance and diabetes mellitus

Objectives: To evaluate biomarkers of endothelial dysfunction and oxidative stress in glucose intolerance (GI) compared to overt diabetes (DM2). Design and methods: 140 volunteers including 96 with DM2, 32 with GI and 12 controls (C) were Studied. NO metabolites, NO synthase inhibitors. thiols and N-acetyl-beta-glucosaminidase (NAGase) activity were analyzed by chemiluminescence, capillary electrophoresis, ELISA and colorimetric assay, respectively. Results: (center dot)NO metabolites were higher in GI (NOx: P=0.03 S-nitrosothiols: p=0.001) and DM2 (p=0.006; p=0.0006) groups in relation to group C, while nitrotyrosine was higher only in the DM2 group in comparison 10 the other groups. NAGase activity was elevated in GI (p=0.003) and DM2 (p=0.0004) groups in relation to group C, as well as, ADMA (p=0.01: p=0.003) and GSSG (p=0.01 p=0.002). Conclusions: (center dot)NO metabolites. (center dot)NO synthase inhibitors. thiols and NAGase are biomarkers Suitable to indicate endothelial dysfunction and oxidative stress in the early stages of impaired response to insulin. (c) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.