Physical activity modulates heat shock protein-72 expression and limits oxidative damage accumulation in a healthy elderly population aged 60 90 years

BACKGROUND: Reactive oxygen species production increases during aging, whereas protective mechanisms such as heat shock proteins (HSPs) or antioxidant capacity are depressed. Physical activity has been hypothesized to provide protection against oxidative damage during aging, but results remain controversial. This study aimed to investigate the effect of different levels of physical activity during aging on Hsp72 expression and systemic oxidative stress at rest and in response to maximal exercise. METHODS: Plasma antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), thiobarbituric acid-reactive species (TBARS), advanced oxidized proteins products (AOPP), and Hsp72 expression in leukocytes were measured before and after maximal exercise testing in 32 elderly persons (aged 73.2 years), who were assigned to two different groups depending on their level of physical activity during the past 12 months (OLow = moderate to low level; OHigh = higher level). RESULTS: The OHigh group showed higher aerobic fitness and TEAC (both representing 120% of OLow values) as well as lower oxidative damage (50% of OLow values) and Hsp72 expression. Exercise led to a lower increase in oxidative damage in the OHigh group. Aerobic fitness was positively correlated with TEAC and negatively with lipid peroxidation (TBARS). Hsp72 expression was negatively correlated with TEAC but positively correlated with TBARS levels. CONCLUSIONS: The key finding of this study is that, in people aged 60 to 90 years, long-term high level of physical activity preserved antioxidant capacity and limited oxidative damage accumulation. It also downregulated Hsp72 expression, an adaptation potentially resulting from lower levels of oxidative damage.

Nrf2 links epidermal barrier function with antioxidant defense.

The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators.

Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia.

Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, a developmental rodent model useful for schizophrenia research. Juvenile and adolescent treatment with the antioxidant N-acetyl cysteine prevented the reduction of prefrontal parvalbumin interneuron activity observed in this model, as well as electrophysiological and behavioral deficits relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase mimic ebselen also reversed behavioral deficits in this animal model. These findings suggest that presymptomatic oxidative stress yields abnormal adult brain function in a developmentally compromised brain, and highlight redox modulation as a potential target for early intervention.

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients.

INTRODUCTION: Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo. RESULTS: Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045). CONCLUSION: The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation. TRIALS REGISTRATION: Clinical Trials.gov RCT Register: NCT00515736.

Effect of potassium sources on the antioxidant activity of eggplant¹

Potassium participates in the essential processes in plant physiology, however, the effects of K sources on plant metabolism have been little studied. Also, in certain cases, K sources and concentrations may cause undesirable effects, e.g., soil salinization. The objective was to evaluate the effect of K sources and levels on the enzyme activity of the antioxidant system and protein content in eggplant (Solanum melongena L.) leaves and to determine the most suitable K sources for these physiological characteristics. The experiment was conducted in randomized blocks, in a 2 × 4 factorial design, consisting of two K sources (KCl and K2SO4) and rates (250, 500, 750, and 1000 kg ha-1 K2O), with four replications. The following variables were evaluated: plant height, number of leaves per plant, superoxide dismutase (SOD), catalase (CAT), and leaf protein content. There was an increase in CAT activity with increasing K levels until 30 days after transplanting (DAT), when K2SO4 was applied and until 60 DAT, when KCl was used; after this period, the enzyme activity decreased under both sources. The activity of SOD increased in the presence of KCl, but was reduced with the application of K2SO4. For both K sources, increasing rates reduced the protein content and number of leaves per plant, and this reduction was greater under KCl application. Thus it was concluded that KCl tends more strongly to salinize the soil than K2SO4. Both for KCl and for K2SO4, the increasing rates adversely affected the activities of CAT and SOD and the levels of leaf protein in eggplant. The potential of KCl to reduce the enzyme activity of SOD and CAT, leaf protein content and plant growth of eggplant was stronger than that of K2SO4.

Monitoring the clinical introduction of a glutamine and antioxidant solution in critically ill trauma and burn patients

OBJECTIVE: Enteral glutamine supplementation and antioxidants have been shown to be beneficial in some categories of critically ill patients. This study investigated the impact on organ function and clinical outcome of an enteral solution enriched with glutamine and antioxidant micronutrients in patients with trauma and with burns. METHODS: This was a prospective study of a historical control group including critically ill, burned and major trauma patients (n = 86, 40 patients with burns and 46 with trauma, 43 in each group) on admission to an intensive care unit in a university hospital (matching for severity, age, and sex). The intervention aimed to deliver a 500-mL enteral solution containing 30 g of glutamine per day, selenium, zinc, and vitamin E (Gln-AOX) for a maximum of 10 d, in addition to control treatment consisting of enteral nutrition in all patients and intravenous trace elements in all burn patients. RESULTS: Patients were comparable at baseline, except for more inhalation injuries in the burn-Gln-AOX group (P = 0.10) and greater neurologic impairment in the trauma-Gln-AOX group (P = 0.022). Intestinal tolerance was good. The full 500-mL dose was rarely delivered, resulting in a low mean glutamine daily dose (22 g for burn patients and 16 g for trauma patients). In burn patients intravenous trace element delivery was superior to the enteral dose. The evolution of the Sequential Organ Failure Assessment score and other outcome variables did not differ significantly between groups. C-reactive protein decreased faster in the Gln-AOX group. CONCLUSION: The Gln-AOX supplement was well tolerated in critically ill, injured patients, but did not improve outcome significantly. The delivery of glutamine below the 0.5-g/kg recommended dose in association with high intravenous trace element substitution doses in burn patients are likely to have blunted the impact by not reaching an efficient treatment dose. Further trials testing higher doses of Gln are required.

The Utilization of Agriculturally Derived Lignin as an Antioxidant in Asphalt Binder, TR-557, 2008

Oxidation is the primary cause of long-term aging in asphalt pavements. As a pavement oxidizes, it stiffens and can eventually crack. The use of an antioxidant as a performance enhancer in an asphalt binder could delay aging, thus increasing the life of an asphalt pavement. Lignin is a highly available and well-studied antioxidant. A wet-mill ethanol plant produces several co-products, some of which contain lignin. The use of lignin from ethanol production could provide a benefit to asphalt pavements and also give more value to the co-products. The following research examined the effects of lignin on asphalt pavements. Three lignin-containing co-products were separately combined with four asphalt binders in varying amounts to determine the optimum amount of co-product that would provide the greatest benefit to the asphalt binders. The asphalt binder and co-product blends were evaluated according to Superpave specifications and performance graded on a continuous scale. The data indicated a stiffening effect on the binder caused by the addition of the co-products. The more a co-product was added, the more a binder stiffened. Binder stiffening benefited the high temperature properties and the low temperature binder properties were negatively affected. However, the low temperature stiffening effects were small and in many cases not significant. The co-products had an overall effect of widening the temperature range of the binders. This result suggests some antioxidant activity between the binder and the lignin. Testing with a fourth co-product with no lignin supported the idea that lignin acts as an antioxidant. The samples with no lignin aged significantly more than the samples with lignin. Infrared spectrometry also supported the idea that lignin acts as an antioxidant by observing decreases in some oxidative aging products.

Effect of an 8-weeks aerobic training program in elderly on oxidative stress and HSP72 expression in leukocytes during antioxidant supplementation.

OBJECTIVE: To investigate the effect of aerobic training in the context of antioxidant supplementation on systemic oxidative stress and leukocytes heat shock protein (Hsp)72 expression in the elderly. DESIGN: Sixteen septuagenarians (8 males and 8 females, mean age 74.6) were supplemented with Vitamin C and E (respectively 500 and 100mg per day) and randomly assigned either to sedentary (AS) or individualized aerobically trained (AT) group for 8 weeks. METHODS: Plasma Vitamin C and E concentrations and aerobic fitness, as well as resting and post graded exercise (GXT) Hsp72 expression in leukocytes, plasma levels of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) were measured pre and post training / supplementation. RESULTS: At the end of the intervention, the two groups showed a significant increase in resting plasma vitamin C and E (approximately 50 and 20% increase respectively) and a significant decrease in both resting and post GXT plasma TBARS and AOPP (approximately 25 and 20% decrease respectively). These changes were of similar magnitude in the two groups. The reduced oxidative stress was concomitant with a 15% decreased expression of Hsp72 in monocytes and granulocytes in both groups. CONCLUSION: This study provides evidence that in elderly, increased concentration of antioxidant vitamins C and E is associated with a reduction in oxidative stress and leukocytes Hsp72. In this context, 8 weeks of aerobic training has no impact on oxidative stress or leukocytes Hsp72 expression in elderly people.

Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells.

Cancer cell metabolism differs from that of non-transformed cells in the same tissue. This specific metabolism gives tumor cells growing advantages besides the effect in increasing anabolism. One of these advantages is immune evasion mediated by a lower expression of the mayor histocompatibility complex class I molecules. The extracellular-signal-regulated kinase-5 regulates both mayor histocompatibility complex class I expression and metabolic activity. However, the mechanisms underlying are largely unknown. We show here that extracellular-signal-regulated kinase-5 regulates the transcription of the NADH(+)-dependent histone deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin 1) in leukemic Jurkat T cells. This involves the activation of the transcription factor myocyte enhancer factor-2 and its binding to the sirt1 promoter. In addition, extracellular-signal-regulated kinase-5 is required for T cell receptor-induced and oxidative stress-induced full Sirtuin 1 expression. Extracellular-signal-regulated kinase-5 induces the expression of promoters containing the antioxidant response elements through a Sirtuin 1-dependent pathway. On the other hand, down modulation of extracellular-signal-regulated kinase-5 expression impairs the anti-oxidant response. Notably, the extracellular-signal-regulated kinase-5 inhibitor BIX02189 induces apoptosis in acute myeloid leukemia tumor cells without affecting T cells from healthy donors. Our results unveil a new pathway that modulates metabolism in tumor cells. This pathway represents a promising therapeutic target in cancers with deep metabolic layouts such as acute myeloid leukemia.

Classification and fingerprinting of different berries based on biochemical profiling and antioxidant capacity

The objective of this work was to evaluate the biochemical composition of six berry types belonging to Fragaria, Rubus, Vaccinium and Ribes genus. Fruit samples were collected in triplicate (50 fruit each) from 18 different species or cultivars of the mentioned genera, during three years (2008 to 2010). Content of individual sugars, organic acids, flavonols, and phenolic acids were determined by high performance liquid chromatography (HPLC) analysis, while total phenolics (TPC) and total antioxidant capacity (TAC), by using spectrophotometry. Principal component analysis (PCA) and hierarchical cluster analysis (CA) were performed to evaluate the differences in fruit biochemical profile. The highest contents of bioactive components were found in Ribes nigrum and in Fragaria vesca, Rubus plicatus, and Vaccinium myrtillus. PCA and CA were able to partially discriminate between berries on the basis of their biochemical composition. Individual and total sugars, myricetin, ellagic acid, TPC and TAC showed the highest impact on biochemical composition of the berry fruits. CA separated blackberry, raspberry, and blueberry as isolate groups, while classification of strawberry, black and red currant in a specific group has not occurred. There is a large variability both between and within the different types of berries. Metabolite fingerprinting of the evaluated berries showed unique biochemical profiles and specific combination of bioactive compound contents.

Anthocyanins, pigment stability and antioxidant activity in jabuticaba [Myrciaria cauliflora (Mart.) O. Berg]

Different solvents were evaluated for the extraction of jabuticaba anthocyanin pigments, identifying, quantifying and verifying the stability of the anthocyanins, as well as the conduction of three antioxidant activity assays and determination of the vitamin C levels. The maceration with ethanol acidified with HCl 1.5 mol L-1 (85:15) provides better pigment extraction and stability. The skin is anthocyanin rich, presenting 1.59 and 2.06 g 100 g-1 of dry matter in the Paulista and Sabará varieties, respectively. Cyanidin 3-glucoside is the majority pigment of the skins, followed by delphinidin 3-glucoside. The highest level of vitamin C was found in the skins and seeds of both varieties. It was verified that the skins, presented more antioxidant activity, in free radical capture, as well as in retarding the lipid oxidation process.

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

Background:Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.

Potential of antioxidant extracts produced by aqueous processing ofrenewable resources for the formulation of cosmetics

The performance of natural extracts obtained from underutilized and residual vegetal and macroalgal biomass processed with food-grade green solvents was compared with that of commercial antioxidants. Selected extracts were obtained from two terrestrial sources: winery byproducts concentrate (WBC) and chestnut burs hydrothermally fractionated extract (CBAE), and from two underutilized seaweeds: Sargassum muticum extracts, either extracted with ethanol (SmEE) or after alginate extraction and hydrothermal fractionation (SmAE) and from Ulva lactuca processed by mild acid extraction and membrane concentration (UlAE). These extracts showed in vitro antioxidant properties comparable to commercial antioxidants and were safe for topical use based on the absence of skin-irritant effects at 0.1% on reconstructed human tissues. The stability of several cosmetic model emulsions was assessed during accelerated oxidation assays. The incorporation of natural extracts produced from renewable underutilized resources at 0.4-0.5% in an oil-in-water emulsions reduced lipid oxidation during storage.

Characterization of the antioxidant capacity of natives fruits from the Brazilian Amazon Region

The objective of the present study was to characterize the chemistry and the antioxidant capacity in 8 species of native fruits from Amazonia. All the fruits were collected at full physiological and commercial maturity from properties located at: Boa Vista / RR, São Luiz do Anauá / RR, Manaus / AM, and Belém / PA. At the end of the experiment, the functional pattern for the camu-camu fruits showed that the total phenolic and ascorbic acid content and antioxidant assays were superior compared to the other samples. Despite the functional losses detected for the freeze-dried samples of the camu-camu fruit, all the other freeze-dried samples kept under -20ºC showed appropriate stability for long-term storage. In addition, it was also observed that fruit peel showed higher antioxidant activity than pulp or samples containing peel and pulp tissues in the same extract. When the ratio between the ORAC and total phenolic assays were observed, the uxi fruit demonstrated the highest antioxidant power compared to the other fruits studied, despite its relatively low levels of phenolic compound content and ORAC values. This means that there is a relevant contribution of these phenolic compounds to the antioxidant activity of uxi fruit.