Properties of Resveratrol:In VitroandIn VivoStudies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlightin…

Frailty Is Associated with Oxidative Stress in Older Patients with Type 2 Diabetes

Aging has increased the prevalence of frailty, and type 2 diabetes (T2D) has also increased in prevalence. Diabetes and oxidative stress (OS) have been shown to be related to frailty. However, the exact mechanism by which it occurs is not fully known. Our aim was to analyze body composition in community-dwelling older diabetic people treated in our center and to evaluate the possible relation between OS, frailty, and body composition. We included 100 adults older than 65 years with T2D. We found that 15% were frail and 57% were prefrail. The patients included in the nonrobust group showed increased levels of OS. Our study shows that the presence of T2D in the geriatric population is associa…

Uso de la infografía en la optativa “Alimentación y Dietética” del grado de Medicina

[ES] Como sustitución de la clase magistral, en la sesión dedicada a tratar las características de “dietas occidentales de moda” de la asignatura optativa 34493-Alimentación y Dietética del Grado en Medicina de la Universitat de Valencia, se utilizaron infografías previamente diseñadas por los estudiantes. Con esta iniciativa se pretendía mejorar la participación del alumnado en la asignatura, además de profundizar en la materia, mejorar sus habilidades digitales y de búsqueda y síntesis de información. Esta propuesta fue bien valorada por el estudiantado, que mostró su preferencia por esta forma de trabajar frente a la clase magistral. Además, opinó que la actividad mejoraba su capacidad d…

Antioxidants in skeletal muscle physiology, a radically different approach.

Regular physical exercise has many health benefits (1). Paradoxically, it is also clear that contracting skeletal muscles generate reactive oxygen species (ROS) and that prolonged and intense exercise can result in oxidative damage to cellular constituents (2-4). Reactive oxygen species production is dependent on the intensity of the exercise with higher amount of ROS generated by strenuous exercise (5, 6). Antioxidants may reduce the adverse effects of exercise-induced ROS (2-4). However, ROS are not only toxic but rather play an important role in cell signalling and in the regulation of gene expression (7, 8) and force production in skeletal muscle (9). Thus, we have recently raised quest…

An overview of doping in sports

The history of doping field can be outlined in three major stages: (1) early stage in which drug abuse took place during sports performance and competition and gas chromatography was used for its detection; (2) approximately in the 1970s when androgenic anabolic steroids were introduced; (3) In the recent era when the fields of biochemistry, physiology, toxicology, genomics, genetics, immunology, and molecular biology were integrated and applied routinely. Advanced omics technology and gene doping age may be applied in near future. This review will discuss commonly abused materials, both their adverse and harmful effects, and the alleged benefits in conjunction with the current standards in…

Roles of sedentary aging and lifelong physical activity in exchange of glutathione across exercising human skeletal muscle.

Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across the leg of young (23±1 years) and older (66±2 years) sedentary humans by measuring the whole blood co…

The hybrid algorithm (Hbmr) to fight against blood doping in sports

A New Frailty Score for Experimental Animals Based on the Clinical Phenotype: Inactivity as a Model of Frailty.

The development of animal models to study human frailty is important to test interventions to be translated to the clinical practice. The aim of this work was to develop a score for frailty in experimental animals based in the human frailty phenotype. We also tested the effect of physical inactivity in the development of frailty as determined by our score. Male C57Bl/6J mice, individually caged, were randomly assigned to one of two groups: sedentary (inactive) or spontaneous wheel-runners. We compared the sedentary versus the active lifestyle in terms of frailty by evaluating the clinical criteria used in humans: unintentional weight loss; poor endurance (running time); slowness (running sp…

Exercise as a calorie restriction mimetic. Implications for the treatment of age associated frailty

The free radical theory of aging has provided a theoretical framework for an enormous amount of work leading to advances in our understanding of aging. A critical blow to the free radical theory of aging came from epidemiological studies showing that antioxidant supplementation did not lower the incidence of age-associated diseases. However, work from many laboratories supports the theory, for instance showing that overexpression of antioxidant enzymes results in increases not only in life-span but also in health-span. Improving healthy aging means delaying disability. Disability is often preceded by a state characterized by reduced capacity to respond to stressors, caused by a decline in f…

Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players

Xanthine oxidase (XO), a free radical-generating enzyme, is involved in tissue damage produced during exhaustive exercise. Our aim was to test whether allopurinol, a powerful inhibitor of XO, may be effective in preventing exercise-induced tissue damage in soccer players. Twelve soccer players were randomized into two experimental groups. One received allopurinol, before a match of the premier Spanish Football League, and the other placebo. Allopurinol prevented the exercise-induced increase in all the markers of skeletal muscle damage analyzed: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and myoglobin. Creatine kinase-MB isoenzyme and highly sensitive troponin T, sp…

Laboratory medicine and sports : between Scylla and Charybdis

Laboratory medicine is complex and contributes to the diagnosis, therapeutic monitoring and follow-up of acquired and inherited human disorders. The regular practice of physical exercise provides important benefits in heath and disease and sports medicine is thereby receiving growing focus from almost each and every clinical discipline, including laboratory medicine. Sport-laboratory medicine is a relatively innovative branch of laboratory science, which can provide valuable contributions to the diagnosis and follow-up of athletic injuries, and which is acquiring a growing clinical significance to support biomechanics and identify novel genomics and "exercisenomics" patterns that can help i…

Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches.

Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria. Cells respond to different physiologic, metabolic, and pathologic changes by regulating this organelle with high morphological and functional adaptability. A considerable number of proteins, transcription factors, upstream regulatory proteins and secondary mechanisms are involved in MB and the stabilization of new mitochondrial DNA. These MB activators and regulators, including the main participating proteins (e.g. PGC-1α and mtTFA), are candidates for therapeutic intervention in diverse diseases, like neurodegenerative disorders, metabolic syndrome, sarcopenia, cardiac pathophysiolo…

Desmopresssin and hemodilution: implications in doping.

Blood doping improves physical performance in sport. This is the reason why the antidop- ing authorities subject athletes to blood tests. Plasma volume expanders are prohibited agents used to reduce an artifi cial increase in hemato- logical values using diff erent illegal practices. The aim of our study was to test whether desmo- pressin (DDAVP)-induced hemodilution would alter the concentration of hematological param- eters used to detect blood doping in sports. This was an intra-subject crossover study. Venous blood samples were obtained from eight physi- cally active males on two occasions. On the fi rst o ccasion the subjects ingested 1.5 L of mineral water and 4.3 μ g / kg of DDAVP. O…

Overexpression of glucose 6 phosphate dehydrogenase preserves mouse pancreatic beta cells function until late in life.

NAD(P)H donates electrons for reductive biosynthesis and antioxidant defense across all forms of life. Glucose-6- phosphate dehydrogenase (G6PD) is a critical enzyme to provide NADPH. G6PD deficiency is present in more than 400 million people worldwide. This enzymopathy provides protection against malaria but sensitizes cells to oxidative stressors. Oxidative stress has been involved in the pathogenesis of the diabetic complications and several studies have provided evidences of a link between G6PD deficiency and type 2 diabetes (T2D). We hypothesized that a moderate overexpression of G6PD (G6PD-Tg) could protect β-cells from age-associated oxidative stress thus reducing the risk of develop…

G6PD Overexpression Protects Mice Against Associated Oxidative Stress and Delays the Occurrence of Frailty

To assess the impact of lifelong overexpression of G6PD on reactive oxygen species (ROS)-derived damage and the prevention of frailty, we measured the levels of macromolecular oxidative damage in young and old mice and the we tested the neuromuscular fitness and the grip strength in old mice. Old G6PD-Tg male and female mice showed diminished accumulation of DNA oxidation (measured as 8-hydroxyguanosine or 8-OHdG) in liver and brain. Old females also showed reduced lipid oxidation (measured as malondialdehyde or MDA) in the liver. Old G6PD-Tg males, but not females, presented a small but significant increase in brain protein carbonylation. In accordance with these findings, liver from 2-yea…

Data on in vivo PGC-1alpha overexpression model via local transfection in aged mouse muscle

The data presented in this article are related to the research paper entitled “Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1alpha overexpression in vivo” (Yeo et al., 2019). The data explained the surgical procedure of in vivo local transfection by electroporation method in aged mouse tibialis anterior muscle, and plasmid DNA preparation and verification protocol. The data also showed the transfection efficiency levels of GFP or GFP-tagged PGC-1alpha through immunohistochemistry method for frozen muscle cross-sections.

A free radical theory of frailty.

The free radical theory of ageing provided an intellectual framework for many laboratories working on ageing. However, experimental and clinical evidence showing that high doses of antioxidants do not have an effect on ageing or on age-associated diseases, cast doubts on the validity of this theory. Data from our own laboratory show that oxidative damage does not correlate with age, especially in the geriatric population, but rather with the frailty state. This has led us to postulate the free radical theory of frailty that proposes that oxidative damage is associated with frailty, but not with chronological age itself. Superoxide dismutase deficient mice are more frail than controls. But m…

Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis

Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study aimed to investigate the contribution of oxidative stress to cancer-induced cachexia in the presence or in the absence of moderate exercise training. Mice bearing the colon C26 carcinoma, either sedentary or exercised, were used. The former showed muscle wasting and redox imbalance, with the activation of an antioxidant response and with upregulation of markers of proteasome-dependent…

Growth hormone replacement therapy prevents sarcopenia by a dual mechanism: improvement of protein balance and of antioxidant defenses.

The aim of our study was to elucidate the role of growth hormone (GH) replacement therapy in three of the main mechanisms involved in sarcopenia: alterations in mitochondrial biogenesis, increase in oxidative stress, and alterations in protein balance. We used young and old Wistar rats that received either placebo or low doses of GH to reach normal insulin-like growth factor-1 values observed in the young group. We found an increase in lean body mass and plasma and hepatic insulin-like growth factor-1 levels in the old animals treated with GH. We also found a lowering of age-associated oxidative damage and an induction of antioxidant enzymes in the skeletal muscle of the treated animals. GH…

Special issue: Exercise redox biology from health to performance

Physical exercise in the prevention and treatment of Alzheimer's disease

Highlights • Low levels of physical activity are a risk factor associated with Alzheimer's disease. • Older adults who exercise are more likely to maintain cognition. • Exercise modulates amyloid β turnover, inflammation, synthesis, and release of neurotrophins, and cerebral blood flow.

Redox modulation of muscle mass and function

Muscle mass and strength are very important for exercise performance. Training-induced musculoskeletal injuries usually require periods of complete immobilization to prevent any muscle contraction of the affected muscle groups. Disuse muscle wasting will likely affect every sport practitioner in his or her lifetime. Even short periods of disuse results in significant declines in muscle size, fiber cross sectional area, and strength. To understand the molecular signaling pathways involved in disuse muscle atrophy is of the utmost importance to develop more effective countermeasures in sport science research. We have divided our review in four different sections. In the first one we discuss t…

Active paraplegics are protected against exercise-induced oxidative damage through the induction of antioxidant enzymes

Exercise improves functional capacity in spinal cord injury (SCI). However, exhaustive exercise, especially when sporadic, is linked to the production of reactive oxygen species that may have a detrimental effect on SCI. We aimed to study the effect of a single bout of exhaustive exercise on systemic oxidative stress parameters and on the expression of antioxidant enzymes in individuals with paraplegia. The study was conducted in the Physical Therapy department and the Physical Education and Sports department of the University of Valencia. Sixteen paraplegic subjects were submitted to a graded exercise test (GET) until volitional exhaustion. They were divided into active or non-active group…

Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart

Aim:  To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart. Methods:  Trained rabbits were submitted to a protocol of treadmill running. The electrophysiological parameters of refractoriness investigated in an isolated heart preparation were: (1) atrial effective refractory period (AERP) and atrial functional refractory period and ventricular effective and functional refractory periods (VERP and VFRP) using the extrastimulus technique at four different pacing cycle lengths; (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi-electrode plaque containing 256 electrodes and a spectral method were used to o…

Reductive stress in pathophysiology

Oxidative stress, as defined by Sies more than thirty years ago, has received much attention and has served as an important intellectual tool to understand the pathophysiology of many diseases and also of normal processes like ageing. However, recently the idea that the cells might suffer from reductive rather than oxidative stress and that such stress may be relevant in pathophysiology has gained momentum. Some time ago we defined reductive stress as a “as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state”. We postulated that reductive stress might be due, at least in part to a “small but persistent generation of oxidants that results i…

Transcriptomic profile of epileptic children treated with ketogenic therapies.

Background: Ketogenic dietary therapies (KDT) are used as a treatment in childhood epilepsy. However, their mechanism has not yet been established. The main objective of this study was to determine the changes in the transcriptomic profile induced by KDT in children with epilepsy in order to shed light on its possible mechanisms. Methods: Eight children with refractory epilepsy were enrolled in the study. Peripheral blood mononuclear cells were obtained before and after the children were treated with KDT for a minimum of 6 months. RNA was extracted and mRNA and miRNA profiling were performed and analyzed. Results: Our intervention with KDT significantly reduced the seizure number in seven o…

Sarcopenia, frailty and their prevention by exercise.

Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people. In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndr…

Alternate methods to prevent protease use as a masking agent in sport.

Increased average longevity among the "Tour de France" cyclists.

It is widely held among the general population and even among health professionals that moderate exercise is a healthy practice but long term high intensity exercise is not. The specific amount of physical activity necessary for good health remains unclear. To date, longevity studies of elite athletes have been relatively sparse and the results are somewhat conflicting. The Tour de France is among the most gruelling sport events in the world, during which highly trained professional cyclists undertake high intensity exercise for a full 3 weeks. Consequently we set out to determine the longevity of the participants in the Tour de France, compared with that of the general population. We studi…

MiRNome of epileptic children suggests the involvement of antioxidant pathways in the neuroprotective role of ketogenic diet

Ketogenic diet (KD) has been used as treatment for refractory epilepsy in children since the 1920s. However, the neuroprotective mechanism of this diet is still unknown. Recent evidence points to a multifactorial effect of KD that involves a decrease of oxidative stress. Mononuclear cells from 14 children with refractory epilepsy, from the Paediatric Hospital “Nino Jesus” in Madrid, were obtained before and after treatment with a ketogenic diet for 6 months. A global analysis of miRNA expression (miRNome) indicates that there are 230 miRNAs which are expressed differently before and after the treatment with KD. If additionally, we restrict the miRNAs with a fold change > |1.3|we obtain 11 r…

Epigenetic biomarkers: A new perspective in laboratory diagnostics.

Epigenetics comprises the study of chemical modifications in the DNA and histones that regulates the gene expression or cellular phenotype. However, during the last decade this term has evolved after the elucidation of different mechanisms (microRNAs and nuclear organization of the chromosomes) involved in regulating gene expression. Epigenetics and the new designed technologies capable to analyze epigenetic changes (e.g., methylated DNA, miRNAs expression, post-translational modifications on histones among others) have disclosed an appealing scenario that will offer for the biomedical sciences new biomarkers for the study of neurodegenerative diseases, multifactorial complex diseases, rare…

Rapid hemodilution induced by desmopressin after erythropoietin administration in humans

We have shown that treatment with desmopressin has a very effective hemodilution effect in healthy humans. These results led us to suggest the possible role of desmopressin to mask blood doping in sports. Based on our results, the World Anti-Doping Agency included the desmopressin in the 2011 List of Prohibited Substances and Methods. On this occasion, the aim of our study was to test the desmopressin-induced hemodilution after rHuEpo administration in humans. This was an intra-subject, crossover study in which five physically active males acted as their own controls. A basal blood sample was taken on their first visit to the laboratory. The next day, the subjects began the treatment. They …

Glucose 6-P dehydrogenase delays the onset of frailty by protecting against muscle damage.

Background: Frailty is a major age-associated syndrome leading to disability. Oxidative damage plays a significant role in the promotion of frailty. The cellular antioxidant system relies on reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is highly dependent on glucose 6-P dehydrogenase (G6PD). The G6PD-overexpressing mouse (G6PD-Tg) is protected against metabolic stresses. Our aim was to examine whether this protection delays frailty. Methods: Old wild-type (WT) and G6PD-Tg mice were evaluated longitudinally in terms of frailty. Indirect calorimetry, transcriptomic profile, and different skeletal muscle quality markers and muscle regenerative capacity were also investigate…

Peripheral Maintenance of the Axis SIRT1-SIRT3 at Youth Level May Contribute to Brain Resilience in Middle-Aged Amateur Rugby Players

Physical exercise performed regularly is known to improve health and to reduce the risk of age-related diseases. Furthermore, there is some evidence of cognitive improvement in physically active middle-aged and older adults. We hypothesized that long-term physically active middle-aged men may have developed brain resilience that can be detected with the analysis of peripheral blood markers. We aimed to analyze the activation of pathways potentially modulated by physical activity in a cohort of healthy amateur rugby players (n = 24) and control subjects with low physical activity (n = 25) aged 45¿65 years. We had previously reported neuropsychological improvement in immediate memory response…

Early reductive stress and late onset overexpression of antioxidant enzymes in experimental myocardial infarction.

Reductive stress is defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. It represents a disturbance in the redox state that is harmful to biological systems. Our aim was to study the occurrence of reductive stress in the early phases of experimental myocardial infarction and to determine the mechanisms leading to such stress using a swine model. During the ischemic period, we found a decrease in the oxidized to reduced glutathione ratio (GSSG/GSH) (0.7-0.3), in the lactate to pyruvate ratio (42.7-132.4), in protein glutathionylation (111.8-96.1), and in p38 phosphorylation (0.9-0.4). This was accompanied by a significant increa…

Exercise as an antioxidant: it up-regulates important enzymes for cell adaptations to exercise

Abstract Aims. – To assess the role of the reactive oxygen species (ROS) in cell signalling and in the regulation of gene expression. Methods. – Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. We have tested this hypothesis by studying the effect of inhibition of ROS production by allopurinol (an inhibitor of xanthine oxidase, a free radical generating enzyme) on cell signalling pathways in marathon runners and in rats submitted to exhaustive exercise by running on a treadmill. Results. – Exercise caused an activation of NF-κB in lymphocytes from marathon runners which wa…

Glucosamine Supplementation Improves Physical Performance in Trained Mice

Introduction D-Glucosamine (GlcN) is one of the most widely consumed dietary supplements and complementary medicines in the world and has been traditionally used to attenuate osteoarthritis in humans. GlcN extends lifespan in different animal models. In humans, its supplementation has been strongly associated with decreased total mortality and improved vascular endothelial function. GlcN acts as a suppressor of inflammation and by inhibiting glycolysis, it can activate the metabolism of stored fat and mitochondrial respiration. Methods The conventional human GlcN dose is 1,500 mg x day-1 but extensive evidence indicates that much higher doses are well tolerated. GlcN is one of the supplemen…

Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation

Skeletal muscle contractions increase superoxide anion in skeletal muscle extracellular space. We tested the hypotheses that 1) after an isometric contraction protocol, xanthine oxidase (XO) activity is a source of superoxide anion in the extracellular space of skeletal muscle and 2) the increase in XO-derived extracellular superoxide anion during contractions affects skeletal muscle contractile function. Superoxide anion was monitored in the extracellular space of mouse gastrocnemius muscles by following the reduction of cytochrome c in muscle microdialysates. A 15-min protocol of nondamaging isometric contractions increased the reduction of cytochrome c in microdialysates, indicating an …

Modulation of ROS levels as a strategy to improve healthy aging

Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1alpha overexpression in vivo.

Mitochondrial dysfunction plays an important role in the etiology of age-related muscle atrophy known as sarcopenia. PGC-1α is positioned at the center of crosstalk in regulating mitochondrial quality control, but its role in mitophagy in aged skeletal muscle is currently unclear. The present study investigated the effects of aging and PGC-1α overexpression via in vivo DNA transfection on key mitophagy protein markers, as well as mitochondrial dynamics related proteins, metabolic function and antioxidant capacity in mouse muscle. C57BL/6J mice at the age of 2 mo (young, Y; N = 14) and 24 mo (old, O; N = 14) were transfected in vivo with either PGC-1α DNA (OE, N = 7) or GFP (N = 7) into the …

Redox-related biomarkers in physical exercise

Research in redox biology of exercise has made considerable advances in the last 70 years. Since the seminal study of George Pake's group calculating the content of free radicals in skeletal muscle in resting conditions in 1954, many discoveries have been made in the field. The first section of this review is devoted to highlight the main research findings and fundamental changes in the exercise redox biology discipline. It includes: i) the first steps in free radical research, ii) the relation between exercise and oxidative damage, iii) the redox regulation of muscle fatigue, iv) the sources of free radicals during muscle contractions, and v) the role of reactive oxygen species as regulato…

Frailty Quantified by the "Valencia Score" as a Potential Predictor of Lifespan in Mice.

The development of frailty scores suitable for mice and which resemble those used in the clinical scenario is of great importance to understand human frailty. The aim of the study was to determine an individual frailty score for each mouse at different ages and analyze the association between the frailty score and its lifespan. For this purpose, the "Valencia Score" for frailty was used. Thus, a longitudinal study in mice was performed analyzing weight loss, running time and speed, grip strength and motor coordination at the late-adult, mature and old ages (40, 56 and 80 weeks old, respectively). These parameters are equivalent to unintentional weight loss, poor endurance, slowness, weaknes…

The COVID-19 pandemic and physical activity

The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease. Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality. The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained…

Modulating Oxidant Levels to Promote Healthy Aging

Significance: Free radicals although originally thought of as damaging molecules, inevitable side effects of the utilization of oxygen by cells, are now considered as signals that by modifying, among others, the thiol-disulfide balance regulate many cell processes from metabolism to cell cycle. Recent Advances: This review discusses the importance of the modulation of the oxidant levels through physiological strategies such as physical exercise or genetic manipulations such as the overexpression of antioxidant enzymes, in the promotion of healthy aging. Critical Issues: We have divided the review into five different sections. In the first two sections of the article "Oxidants are signals" a…

Acute exercise activates nuclear factor (NF)-kappaB signaling pathway in rat skeletal muscle.

Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein kappaB (NF-kappaB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline (C) and killed at resting condition. Ex rats showed higher levels of NF-kappaB b…