Benedito Pereira

Are free radicals involved in lead poisoning

1. The enolamine form of 5-aminolaevulinic acid (ALA), a haem precursor that accumulates in lead poisoning and in acute intermittent porphyria (AIP), undergoes fast autoxidation at slightly alkaline pH with concomitant generation of reactive oxygen species. 2. The transmembrane potential, Ca2+ ion fluxes and state-4 respiratory rate, of isolated rat liver mitochondria are severely affected by mM addition of ALA; the toxic role of ALA-produced oxygen radicals was demonstrated by use of appropriate scavengers. 3. Induction of superoxide dismutase biosynthesis in lead-exposed workers, in AIP carriers and in ALA-treated rats, is viewed as a protective response against oxygen radical toxicity. 4. 5-Aminolaevulinic acid-generated oxygen radicals, together with Pb-stimulated Fe-dependent lipid peroxidation, might be involved in the aetiology of the neuropsychiatric manifestations of both plumbism and acute intermittent porphyria.

Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages

This study examined the effects of glycocorticoids, insulin, thyroxine, and epinephrine upon the activities of CuZn- and Mn-superoxide dismutases (SOD), catalase, and glutathione peroxidase (GPX) and upon hydrogen peroxide production in rat macrophages obtained from the intraperitoneal cavity. The experiments were performed in vivo under conditions causing hormonal dysfunctions: adrenal demedullation, dexamethasone treatment, thyroidectomy, administration of L-tri-iodothyronine (T3) and L-thyroxine (T4), and diabetes. Macrophages were also cultured for 24 hr in the presence of dexamethasone, thyroid hormones, and insulin as to evaluate possible interferences caused in vivo by changes in other hormones. The results indicated that these hormones do control the activities of the antioxidant enzymes and hydrogen peroxide production both in vivo and in vitro. Insulin increased the activities of CuZn-SOD, catalase, and GPX and reduced that of Mn-SOD. Thyroid hormones raised the activities of CuZn- and Mn-SOD and decreased that of GPX, whereas glucocorticoids reduced both Mn-SOD and GPX. The removal of the adrenal medulla caused a decrease of Mn-SOD and GPX activities in the macrophages. Hydrogen peroxide production was increased by insulin and reduced by thyroid hormones and glucocorticoids. The changes in antioxidant enzyme activities caused by these hormones in macrophages may indicate important mechanisms for the establishment of impaired immune function in endocrine pathologies.

Superoxide dismutase, catalase, and glutathione peroxidase activities in muscle and lymphoid organs of sedentary and exercise-trained rats

The effect of swimming-training upon the activities of the enzymes involved in the generation of reducing-equivalents (citrate synthase-mitochondria and glucose-6-phosphate dehydrogenase-cytosol) and of antioxidant enzymes (CuZn- and Mn-SOD, catalase and glutathione peroxidase) in the lymphoid organs (thymus, mesenteric lymph nodes and spleen) was examined. The skeletal muscles (soleus-red and gastrocnemius-white) were also studied. Although our data suggest an apparently random, organ-specific change in enzymatic activity, some interesting trends can be observed. Firstly, the increased citrate synthase and Mn-SOD activities observed in red, but not in white muscle, corroborate the well-known effect of endurance exercise-training on mitochondrial oxidative metabolism. Secondly, there was an inverse relationship between TBARs-monitored lipoperoxidation and glutathione peroxidase activity in all tissues studied, what is in accordance with the previous findings showing that such enzyme exerts the fine control of intracellular lipoperoxide concentration. Except in the case of the spleen, there was a trend for elevated glucose-6-phosphate dehydrogenase activity, coadjuvant of glutathione peroxidase in the antioxidant response to physical exercise in all tissues. Thirdly, Mn-SOD and catalase were conspicuously associated to oxidative stress in the thymus, while glutathione and catalase could be linked to this parameter in the spleen. Fourthly, the lymph nodes seem to be more dependent on the glucose-6-phosphate dehydrogenase/glutathione peroxidase pair for protection against damage promoted by physical exercise. Mn-SOD and catalase activities were lower in the lymph nodes after swimming training.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison between constant and decreasing rest intervals: influence on maximal strength and hypertrophy.

de Souza Jr, TP, Fleck, SJ, Simão, R, Dubas, JP, Pereira, B, de Brito Pacheco, EM, da Silva, AC, and de Oliveira, PR. Comparison between constant and decreasing rest intervals: influence on maximal strength and hypertrophy. J Strength Cond Res 24(7): 1843-1850, 2010-Most resistance training programs use constant rest period lengths between sets and exercises, but some programs use decreasing rest period lengths as training progresses. The aim of this study was to compare the effect on strength and hypertrophy of 8 weeks of resistance training using constant rest intervals (CIs) and decreasing rest intervals (DIs) between sets and exercises. Twenty young men recreationally trained in strength training were randomly assigned to either a CI or DI training group. During the first 2 weeks of training, 3 sets of 10-12 repetition maximum (RM) with 2-minute rest intervals between sets and exercises were performed by both groups. During the next 6 weeks of training, the CI group trained using 2 minutes between sets and exercises (4 sets of 8-10RM), and the DI group trained with DIs (2 minutes decreasing to 30 seconds) as the 6 weeks of training progressed (4 sets of 8-10RM). Total training volume of the bench press and squat were significantly lower for the DI compared to the CI group (bench press 9.4%, squat 13.9%) and weekly training volume of these same exercises was lower in the DI group from weeks 6 to 8 of training. Strength (1RM) in the bench press and squat, knee extensor and flexor isokinetic measures of peak torque, and muscle cross-sectional area (CSA) using magnetic resonance imaging were assessed pretraining and posttraining. No significant differences (p ≤ 0.05) were shown between the CI and DI training protocols for CSA (arm 13.8 vs. 14.5%, thigh 16.6 vs. 16.3%), 1RM (bench press 28 vs. 37%, squat 34 vs. 34%), and isokinetic peak torque. In conclusion, the results indicate that a training protocol with DI is just as effective as a CI protocol over short training periods (6 weeks) for increasing maximal strength and muscle CSA; thus, either type of program can be used over a short training period to cause strength and hypertrophy.

Exercício físico e estresse oxidativo: efeitos do exercício físico intenso sobre a quimioluminescência urinária e malondialdeído plasmático

Estudos tem demonstrado que o exercicio fisico intenso provoca estresse oxidativo em animais e humanos, estando possivelmente relacionado, por exemplo, com fadiga e lesoes teciduais. Por outro lado, poucos estudos relatam a sua ocorrencia em atletas sob treinamento intenso, principalmente devido a problemas metodologicos. O presente estudo teve como objetivo, portanto, estudar em atletas a possivel ocorrencia de lesoes oxidativas em lipideos em decorrencia do exercicio fisico ou do treinamento atraves da quantificacao da quimioluminescencia urinaria e malondialdeido (MDA) plasmatico. Os exercicios utilizados foram: a) corrida na esteira rolante (25-30min), com a quantificacao de ambos os parâmetros e da capacidade antioxidante plasmatica total; b) corrida de 20km realizada por maratonistas; c) treinamento intervalado intenso realizado por corredores de 400m rasos; d) jogo de futebol com 50min de duracao; e e) treinamento de forca/musculacao com e sem suplementacao com creatina. Nos quatro ultimos itens, somente a quimioluminescencia urinaria foi avaliada. As condicoes em que se notou elevacao significativa na quimioluminescencia urinaria apos a realizacao do exercicio sao: a) corrida de 20km; b) jogo de futebol; e c) treinamento de forca/musculacao sem suplementacao com creatina. A corrida na esteira promoveu aumento na concentracao plasmatica de MDA durante e apos a sua realizacao; a capacidade antioxidante plasmatica total modificou-se de forma inversamente proporcional ao aumento no MDA. Os exercicios praticados pelos atletas neste trabalho provocaram estresse oxidativo de maneira diferente, estando possivelmente relacionado com a duracao e a intensidade dos mesmos, e nao somente com a intensidade. Neste trabalho tambem se constatou que o consumo de creatina associado ao treinamento de forca/musculacao pode atuar como antioxidante.Several studies have demonstrated that intense physical exercise causes oxidative stress in animals and humans, being possibly related, for instance, to fatigue and tissue lesions. However, the effects of high intensity exercise or training performed by athletes on the occurrence of oxidative stress are not fully clear, possibly due to methodological limitations. The objective of this study was to identify the occurrence of oxidative lesions in lipids due to physical training in athletes, through the quantification of the urinary chemiluminescence and plasmatic malondialdehyde (MDA). Post-exercise samples were collected after four training protocols: a) treadmill running (25-30 min); b) 20 km running performed by marathon runners; c) interval training accomplished by 400 m runners; d) soccer game with 50 min duration; and e) strength training with and without creatine supplementation. In the last four items, only the urinary chemiluminescence was evaluated. The conditions that presented elevation in urinary chemiluminescence after exercise completion were: a) 20 km running; b) soccer game; and c) strength training without creatine supplementation. The treadmill running increased plasmatic MDA concentration during and after its performance, and the plasmatic antioxidant capacity had an inverse behavior compared to the increase in MDA. The exercise used in this work promoted oxidative stress in a different way and this may be related to the duration and the intensity performed by athletes, and not only to intensity. In this work it was also observed that creatine ingestion associated with strength training might work as antioxidant.

Astaxanthin Supplementation Delays Physical Exhaustion and Prevents Redox Imbalances in Plasma and Soleus Muscles of Wistar Rats

Astaxanthin (ASTA) is a pinkish-orange carotenoid commonly found in marine organisms, especially salmon. ASTA is a powerful antioxidant and suggested to provide benefits for human health, including the inhibition of LDL oxidation, UV-photoprotection, and prophylaxis of bacterial stomach ulcers. Exercise is associated to overproduction of free radicals in muscles and plasma, with pivotal participation of iron ions and glutathione (GSH). Thus, ASTA was studied here as an auxiliary supplement to improve antioxidant defenses in soleus muscles and plasma against oxidative damage induced by exhaustive exercise. Long-term 1 mg ASTA/kg body weight (BW) supplementation in Wistar rats (for 45 days) significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP) and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion. We also provided significant discussion about a putative “mitochondrial-targeted” action of ASTA based on previous publications and on the positive results found in the highly mitochondrial populated (oxidative-type) soleus muscles here.

Antioxidant enzyme activities in the lymphoid organs and muscles of rats fed fatty acids-rich diets subjected to prolonged physical exercise-training.

Rats weighing 45-50 g were fed 3 diets for 8 wk: a balanced control diet (CD) consisting of 4% fat (polyunsaturated/saturated fatty acids [P/S] ratio 2.9/1) and two fat-rich diets: polyunsaturated (UD)--P/S 7.6/1 and saturated (SD) P/S 0.3/1. After 8 wk feeding on the respective diets, rats were subjected to swimming for 90 min at 30 degrees C daily, 5 d/wk for 8 wk. At the end of this period, the rats were killed and the lymphoid organs (LO--thymus, spleen, and mesenteric lymph nodes) and muscles (soleus and gastrocnemius) removed for the measurement of TBARs (Thiobarbituric Acid Reactant Substances) content and of the activities of antioxidant enzymes (CuZn- and Mn-Superoxide dismutase--SOD--, catalase, and glutathione peroxidase). To evaluate the changes in the sites of generation of reducing equivalents involved in the formation of free radicals, the activities of citrate synthase and glucose-6-phosphate dehydrogenase were measured. The exercise-training clearly modified the enzyme activities and TBARs content of the lymphoid organs and skeletal muscles, but this effect was dependent upon the diet given to the rats. However, fatty acid rich diets had presented a more pronounced effect on the studied aspects than did physical activity. Although one could expect a summatory effect of polyunsaturated fatty acid-rich diet and exercise-training, swimming increased the activities of CuZn- and Mn-SOD in almost all tissues from the elevated level promoted by fat-rich diets.

Hemodynamic Behavior During Hemodialysis: Effects of Dialysate Concentrations of Bicarbonate and Potassium

Background/Aims: Ultrafiltration that occurs during hemodialysis (HD) promotes profound alterations in a relatively short period of time. The dialysate content of bicarbonate (DBic) and potassium (DK) may have impact over intradialytic hemodynamics, which goes beyond ultrafiltration, and its impact was evaluated in a prospective cohort. Methods: 30 patients under HD were submitted to hemodynamic assessment (HA) at the beginning and at the end of HD sessions, through a non-invasive method. Serum minus dialysate potassium concentration was expressed as K-Gap. Cardiac index (CI) and peripheral arterial resistance (PAR) variation (post-HD minus pre-HD) were expressed as ΔCI and ΔPAR. Dialysate content of sodium and calcium were expressed as DNa and DCa, respectively. Results: Mean DNa, DK and DBic were, respectively, 136.4 ± 1.1, 2.1 ± 0.6 and 38.2 ± 2.1 mEq/L. In 15 patients, DCa was >1.5 mmol/L and in the other 15 patients ≤ 1.5 mmol/L. The K-Gap ranged from 1.4 to 5.1 mEq/l (median 3.0 mEq/L). There was a reduction in post-HD CI and systolic blood pressure (ΔCI = -0.72l/min/m2 and -11.3±15.1mmHg, respectively, p<0.001 for both). Conversely, PAR increased (ΔPAR = 272dyn.s/cm5, p<0.001). Lower post-HD CI was was associated to higher DBic (p=0.0013) and lower K-Gap (p=0.026). In multivariate analysis, ΔCI was dependent on DBic and K-Gap, whereas ΔPAR was dependent on dialysate calcium during HD. Conclusion: We confirmed that Na and Ca dialysate content exerts and important role on hemodynamic during HD. In addition, our findings pointed out that higher dialysate concentrations of bicarbonate and potassium promote lower cardiac performance at the end of hemodialysis session.

Ankle-Brachial Index: A Simple Way to Predict Mortality among Patients on Hemodialysis - A Prospective Study

Background Ankle-brachial index (ABI) can access peripheral artery disease and predict mortality in prevalent patients on hemodialysis. However, ABI has not yet been tested in incident patients, who present significant mortality. Typically, ABI is measured by Doppler, which is not always available, limiting its use in most patients. We therefore hypothesized that ABI, evaluated by a simplified method, can predict mortality in an incident hemodialysis population. Methodology/Principal Findings We studied 119 patients with ESRD who had started hemodialysis three times weekly. ABI was calculated by using two oscillometric blood pressure devices simultaneously. Patients were followed until death or the end of the study. ABI was categorized in two groups normal (0.9–1.3) or abnormal (<0.9 and >1.3). There were 33 deaths during a median follow-up of 12 months (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality in a multiple regression analysis. Conclusions An easy and inexpensive technique to measure ABI was tested and showed to be significant in predicting mortality. Both low and high ABI were associated to mortality in incident patients on hemodialysis. This technique allows nephrologists to identify high-risk patients and gives the opportunity of early intervention that could alter the natural progression of this population.

Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test.

BackgroundDietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20 g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1 ± 5.8 years old) immediately before and 5 and 60 min after the exhaustive Wingate test.ResultsMaximum anaerobic power was improved by acute creatine supplementation (10.5 %), but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP), leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects.ConclusionsOur data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent) and inherent antioxidant activity of creatine.