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El objetivo de este estudio fue investigar los efectos de la terapia con diodos emisores de luz (LED) en los marcadores de rendimiento físico, daño muscular, inflamación y estrés oxidativo hasta 24 horas después del protocolo de carrera intermitente específico para fútbol sala (Futsal-Specific Intermittent Shuttle Protocol, FISP). Diez jugadores de fútbol sala adultos realizaron el FISP con siete días de diferencia. Los participantes fueron aleatorizados en dos grupos que recibieron LED (630 nm; 300 mW; 4.6 J/cm2, 6 J por punto, 120 J en cada muslo) o placebo. Durante los FISP se determinaron la frecuencia cardíaca (FC) y la concentración sanguínea de lactato [Lac]. Se recogieron muestras de sangre para analizar la creatina cinasa (CK), interleucina-6 (IL-6), factor de necrosis tumoral alfa (TNF-α) y productos avanzados de la oxidación de proteínas (PAOP), y el salto con contramovimiento (CMJ, por sus siglas en inglés) y el dolor muscular percibido se evaluaron antes (Pre), después (Post) y 24 horas después (24 h) del FISP. Los grupos de LED y placebo presentaron valores medios similares de FC (p = .58) y [Lac] (p = .86) durante los FISP. Se observaron efectos de interacción (p < .01) y tiempo (p < .01) en la CK, con un aumento de CK con placebo (p < .01) y LED (p < .01) en el momento Post comparado con el Pre. Se observó un efecto de tiempo en el CMJ (p < .01) y la IL-6 (p < .01); el CMJ presentó valores más bajos en el momento Post (p < .01) y 24 h (p = .01) comparado con Pre, y la IL-6 aumentó en el momento Post comparado con Pre (p < .01) y volvió a valores Pre 24 h después del FISP. No se comunicaron efectos de interacción, tiempo y grupo en relación con el dolor muscular, el TNF-α αo los PAOP (p > .05). En conclusión, la terapia con LED alteró el patrón de la CK después del FISP, pero no cambió los marcadores de rendimiento físico, dolor muscular, inflamación o estrés oxidativo de jugadores de fútbol sala hasta 24 horas después del FISP.

Cigarette smoke (CS) exposure reduces skeletal muscle function; however, the mechanisms involved have been poorly investigated. The current study evaluated the temporal effects of aerobic exercise training on oxidant and antioxidant systems as well as inflammatory markers in skeletal muscle of mice exposed to CS. Mice were randomly allocated to control, exercise, smoke, and smoke+exercise groups and 3 time points (4, 8, and 12 weeks; n = 12 per group). Exercise training and CS exposure were performed for 30 min/day, twice a day, 5 days/week for 4, 8, and 12 weeks. Aerobic exercise improved functional capacity and attenuated the increase in the cachexia index induced by CS exposure after 12 weeks. Concomitantly, exercise training downregulated tumor necrosis factor α concentration, glutathione oxidation, and messenger RNA (mRNA) expression of Keap1 (P < 0.01) and upregulated interleukin 10 concentration, total antioxidant capacity, and mRNA expression of Nrf2, Gsr, and Txn1 (P < 0.01) in muscle. Exercise increased mRNA expression of Hmox1 compared with the control after 12 weeks (P < 0.05). There were no significant differences between smoke groups for superoxide dismutase activity and Hmox1 mRNA expression. Exercise training improved the ability of skeletal muscle to adequately upregulate key antioxidant and anti-inflammatory defenses to detoxify electrophilic compounds induced by CS exposure, and these effects were more pronounced after 12 weeks. Novelty Exercise attenuates oxidative stress in skeletal muscle from animals exposed to CS via Nrf2 and glutathione pathways. Exercise is a helpful tool to control the inflammatory balance in skeletal muscle from animals exposed to CS. These beneficial effects were evident after 12 weeks.

Malathion is an organophosphate insecticide used in agriculture and for controlling vector-borne diseases such as Zika. Humans can be exposed to malathion by means of ingestion of contaminated food. The juvenile and peripubertal periods are a large window of vulnerability to the action of toxic agents. The aim of the present study was to evaluate the effects of low doses of malathion during the development of testes in the juvenile and peripubertal periods in rats. For this purpose, 45 male Wistar rats (postnatal day (PND) 25) were assigned to 3 experimental groups and treated for 40 days. The animals were exposed daily to malathion 10 mg/kg (M10 group) or 50 mg/kg (M50 group) diluted in 0.9 % saline via gavage. The control group received only the vehicle. On the 40th experimental day, the rats were anaesthetized and euthanized. The blood was collected for determination of testosterone concentration. The testes were removed and weighed. Spermatozoa from the vas deferens were used for sperm morphological analysis. The testes were used for evaluation of sperm count and oxidative stress status to determine the inflammatory profile and analysis of tissue constitution. The results showed that both malathion doses reduced the sperm count and increased the number of abnormal sperms. Furthermore, both doses altered the spermatogenetic process, delayed spermiogenesis, reduced the Leydig and Sertoli cell number and increased the thickness of tunica albuginea. The M10 group presented increased IL-10 levels and reduced GSH levels. These parameters did not change in the M50 group. However, the M50 group showed an increase in the number of abnormal seminiferous tubules, a decrease in plasma testosterone concentration and an increase in lipid peroxidation in the testes. In conclusion, the exposure to low doses of malathion during juvenile and peripubertal development resulted in testicular toxicity and compromised the testicular morphology and function.

Ryanodine receptor type-1 (RYR1) and Calsequestrin-1 (CASQ1) proteins, located in the sarcoplasmic reticulum (SR), are two of the main players in skeletal excitation–contraction (EC) coupling. Mutations in the human RYR1 gene (encoding for the SR Ca2+ release channel) and ablation in mice of CASQ1 (a SR Ca2+ binding protein) cause hypersensitivity to halogenated anesthetics (malignant hyperthermia [MH] susceptibility) and to heat (heat stroke; HS). As both MH and HS are characterized by excessive cytosolic Ca2+ levels and hypermetabolic responses, we studied the metabolism of 4-mo-old mice from two different lines that are MH/HS susceptible: knock-in mice carrying a human MH mutation (RYR1YS) and CASQ1-knockout (ko) mice. RYR1YS and, to a lesser degree, CASQ1-null mice show an increased volume of oxygen consumption (VO2) and a lower respiratory quotient (RQ) compared with WT mice (indicative of a metabolism that relies more on lipids). This finding is accompanied by a reduction in total body fat mass in both Y522S and CASQ1-null mice (again, compared with WT). In addition, we found that RYR1YS and CASQ1-null mice have an increased food consumption (+26.04% and +25.58% grams/day, respectively) and higher basal core temperature (+0.57°C and +0.54°C, respectively) compared with WT mice. Finally, Western blots and electron microscopy indicated that, in hyperthermic mice, (1) SERCA (used to remove myoplasmic Ca2+) and UCP3 (responsible for a thermogenic process that dissipates mitochondrial H+ gradient) are overexpressed, and (2) mitochondrial volume and percentage of damaged mitochondria are both increased. In conclusion, the MH/HS phenotype in RYR1YS and CASQ1-null mice is associated with an intrinsically increased basal metabolism.

Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals' life span.Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology.Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff-Bloom-Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span.RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization.

Made available in DSpace on 2022-04-29T08:30:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 Purpose This study aimed to determine the role of mammalian target of rapamycin (mTORC1) activation and catabolic markers in resistance training's (RT) antiatrophy effect during cachexia-induced muscle loss. Methods Myofiber atrophy was induced by injecting Walker 256 tumor cells into rats exposed or not exposed to the RT protocol of ladder climbing. The role of RT-induced anabolic stimulation was investigated in tumor-bearing rats with the mTORC1 inhibitor rapamycin, and cross-sectional areas of skeletal muscle were evaluated to identify atrophy or hypertrophy. Components of the mTORC1 and ubiquitin-proteasome pathways were assessed by real-time polymerase chain reaction or immunoblotting. Results Although RT prevented myofiber atrophy and impaired the strength of tumor-bearing rats, in healthy rats, it promoted activated mTORC1, as demonstrated by p70S6K's increased phosphorylation and myofiber's enlarged cross-sectional area. However, RT promoted no changes in the ratio of p70S6K to phospho-p70S6K protein expression while prevented myofiber atrophy in tumor-bearing rats. Beyond that, treatment with rapamycin did not preclude RT's preventive effect on myofiber atrophy in tumor-bearing rats. Thus, RT's ability to prevent cancer-induced myofiber atrophy seems to be independent of mTORC1's and p70S6K's activation. Indeed, RT's preventive effect on cancer-induced myofiber atrophy was associated with its capacity to attenuate elevated tumor necrosis factor a and interleukin 6 as well as to prevent oxidative damage in muscles and an elevated abundance of atrogin-1. Conclusions By inducing attenuated myofiber atrophy independent of mTORC1's signaling activation, RT prevents muscle atrophy during cancer by reducing inflammation, oxidative damage, and atrogin-1 expression. Department of Physical Education State University of Londrina Department of Physical Education Universidade Estadual Paulista (UNESP) Presidente Prudente Federal University of Mato Grosso Graduate Program of Health Sciences Faculty of Medicine State University of Londrina Department of General Pathology University of Porto Ciafel Faculty of Sport Department of Physical Education Universidade Estadual Paulista (UNESP) Presidente Prudente

Objetivo: Investigar a função pulmonar, aptidão cardiorrespiratória e o efeito agudo do exercício físico no comportamento do sistema oxidante e antioxidante de indivíduos diabéticos. Métodos: Pesquisa experimental, com indivíduos de ambos os sexos, divididos em dois grupos: controle-GC (n=17) e diabético- GD (n=16). Foram avaliados quanto à função pulmonar (manovacuometria, cirtometria e pico de fluxo expiratório - PFE) e aptidão cardiorrespiratória (distância percorrida no teste de caminhada de seis minutos- dpTC6). O efeito agudo do exercício físico nos sistemas oxidantes e antioxidantes foram mensurados através da glicemia, lipoperoxidação de membrana (LPO) e capacidade antioxidante total (TRAP) foram mensuradas antes e após uma sessão de exercício físico (TC6). Resultados: Houve diminuição da mobilidade axilar e xifoidiana, pico de fluxo expiratório e TRAP no GD (p

Objectives This study aimed to analyze the effect of creatine (Cr) supplementation on tumor microenvironment, evaluating the parameters of tumor aggressiveness. Methods Sixteen male Wistar rats were randomly assigned to 2 groups (n = 8/group): Tumor-bearing (T) and tumor-bearing supplemented with Cr (TCr). Cr supplementation was provided in drinking water for a total of 21 d. After 11 d of Cr supplementation (TCr group) or water (T group), Walker-256 tumor cells were inoculated subcutaneously in the right flank of all rats, which kept receiving Cr supplementation (TCr group) or water (T group) for 10 more days. The total period of the experiment was 21 d. Results Tumor weight corresponded with approximately 3.5% ± 0.9% of animal body weight in the T group. Cr supplementation did not accelerate tumor growth or increase tumor size. The histopathological analysis demonstrated the presence of nuclear pleomorphisms and atypical nuclei, with the presence of low-differentiated tumor cells, in both groups. Cr supplementation did not alter apoptosis and cell proliferation markers, nor tumor capsule thickness and viable tumor area. Conclusions Cr supplementation in Walker-256 tumor-bearing rats did not induce significant changes in tumor development, and did not interfere with the parameters of tumor aggressiveness, such as the level of cell differentiation and proliferation.

Spermatogenesis and steroidogenesis are not fully established during puberty. Especially during this period, children and adolescents may be chronically sleep deprived due to early school hours and constant exposure to artificial light and interactive activities. We have previously shown that sleep restriction (SR) during peripuberty impairs sperm motility and has consequences on epididymal development in rats. Thus, this study aimed to evaluate the effect of SR during peripuberty on sexual hormones and its impact on testicular tissue. Rats were subjected to 18 h of SR per day for 21 days or were maintained as controls (C) in the same room. The circulating luteinizing hormone levels were decreased in SR rats without changes in the follicle stimulating hormone levels. Plasma and intratesticular testosterone and corticosterone in the SR group were increased in relation to C group. These alterations impair testicular tissue, with decreased IL-1β, IL-6, and TNFα levels in the testis and diminished seminiferous epithelium height and Sertoli cell number. SR also increased testicular lipid peroxidation with no alteration in antioxidant profiles. There were no significant changes in sperm parameters, seminiferous tubule diameter, histopathology, spermatogenesis kinetics, neutrophil and macrophage recruitment, and IL-10 concentration. Our results show that SR unbalances sexual hormones and testicular cytokines at a critical period of sexual maturation. These changes lead to lipid peroxidation in the testes and negatively influence the testicular tissue, as evidenced by diminished seminiferous epithelium height-with apoptosis of germinative cell-and Sertoli cell number.

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk ( P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk ( P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs ( P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk ( P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation. NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.

Purpose: To analyze the muscle changes with high-intensity aerobic training (HIAT) in an animal model of renal disease (RD). Methods: Twenty one adult Wistar rats were divided into 3 groups: healthy sedentary (HS), RD sedentary (RDS), RD aerobic training (RDAT). RDS and RDAT were subjected to unilateral renal ischemia-reperfusion (10 min) and 21days after that, RDAT was subjected to 6 weeks HIAT (swimming). Serum creatinine (Cr) and muscle morphometry (cross-sectional area = CSA) of gastrocnemius were analyzed. Results: Cr was higher (p = 0.0053) in RDS (0.82 ± 0.04) than in the others (RDAT 0.55 ± 0.04; HS 0.55 ± 0.04). Morphometric analysis (class interval of CSA in μm2/absolute frequency of muscle fibers in each class) indicated that 50th percentile occurred in: HS 7th class (3000.00-3499.00/515), RDS, 8th class (3500.00-3999.00/484), RDAT 5th class (2000.00-2499.00/856). CSA of largest fibers in RDS, RDAT, HS was 9953.00 μm2, 9969.00 μm2,11228.00 μm2, respectively. High frequency of fibers with lower CSA occurred in 4th, 5th, 6th and 7th class in RDA, absence of fibers into 22nd, 23rd classes (RDS and RDAT). Conclusion: HIAT in an animal model of RD resulted in increased the number of muscle fibers with smaller CSA.

The aim of this study was to investigate changes in homocysteine (Hcy) metabolism and redox balance in response to exercise treatment in a tumor-bearing rat model.Male Wistar rats were exposed, or not, to a resistance exercise program 6 wk before inoculation with Walker-256 tumor cells or vehicle. After application, rats maintained their routine for 12 d and were then sacrificed for plasma and liver analyses.Impaired Hcy metabolism was evident after 12 d of tumor cell inoculation as demonstrated by significantly increased (P 0.05) plasma total homocysteine (tHcy) concentration (53%) and decreased plasma cysteine, methionine, and vitamin B12 concentrations. Decreased hepatic cystathionine β-synthase (CBS) and betaine-homocysteine S-methyltransferase mRNA levels were found in tumor-bearing rats but not in controls. Tumor inoculation also decreased levels of liver reduced glutathione (GSH) and increased hepatic oxidative stress compared with non-tumor controls. However, resistance exercise prevented the tumor-impaired transsulfuration pathway as demonstrated by the decreased plasma tHcy, hepatic CBS expression, and increased GSH in tumor-exercised versus tumor-sedentary rats. Remarkably, all measures of liver oxidative stress were suppressed by exercise training. Tumor weight was unchanged between groups.Resistance exercise prevented tHcy accumulation and liver oxidative damage caused by Walker-256 tumor cell inoculation; the modulatory effects of resistance exercise on Hcy metabolism appear to be at the level of transsulfuration pathway.

Aims Well-characterized animal tumor models of cancer cachexia are warranted to elucidate underlying mechanisms and provide a better approach to the human scenario. We aimed to investigate whether solid Ehrlich carcinoma reproduces clinical, functional and biological conditions of tumor-induced cachexia in mice. Methods Eight-week old female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells (tumor-bearing, TB group) or vehicle (sham) into the right flank and monitored for 28 days. Tumor histopathological features and tumor–host interaction, including tissue weight, muscle structure, strength and biochemical parameters were carried out. Key findings Tumor growth curve demonstrated a linear pattern with no difference in final carcass weight between groups. A well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The TB group had reduced handgrip strength, aside from lower cross sectional area (CSA) and critically reduced parametrial fat pads. Plasma parameters of lactate dehydrogenase (LDH), creatine kinase (CK) and tumor necrosis factor-α (TNF-α) were higher in the TB group, suggesting predominance of catabolic and pro-inflammatory activities. Conversely, food intake and tissue weight did not differ between groups. Significance Our data elucidated that the solid Ehrlich tumor model is feasible and effective in reproducing some of the relevant issues experienced by cancer patients with cachexia. The solid Ehrlich carcinoma emerges as an alternative tool against more aggressive cancer cachexia models during preclinical research.

In fast-twitch fibers from adult mice Ca2+ release units (CRUs, i.e. intracellular junctions of excitation-contraction coupling), and mitochondria are structurally linked to each other by small strands, named tethers. We recently showed that aging causes separation of a fraction of mitochondria from CRUs and a consequent impairment of the Ca2+ signaling between the two organelles. However, whether the uncoupling of mitochondria from CRUs is the result of aging per-se or the consequence of reduced muscle activity remains still unclear. Here we studied the association between mitochondria and CRUs: in a) extensor digitorum longus (EDL) muscles from 2 years old mice, either sedentary or trained for 1 year in wheel cages; and b) denervated EDL muscles from adult mice and rats. We analyzed muscle samples using a combination of structural (confocal and electron microscopy), biochemical (assessment of oxidative stress via western blot), and functional (ex-vivo contractile properties, and mitochondrial Ca2+ uptake) experimental procedures. The results collected in structural studies indicate that: a) ageing and denervation result in partial uncoupling between mitochondria and CRUs; b) exercise either maintains (in old mice) or restores (in transiently denervated rats) the association between the two organelles. Functional studies supported the hypothesis that CRU-mitochondria coupling is important for mitochondrial Ca2+ uptake, optimal force generation, and muscle performance. Taken together our results indicate that muscle activity maintains/improves proper association between CRUs and mitochondria.

Muscle wasting or atrophy is extensively associated with human systemic diseases including diabetes, cancer, and kidney failure. Accumulating evidence from transcriptional profiles has noted that a common set of genes, termed atrogenes, is modulated in atrophying muscles. However, the transcriptional changes that trigger the reversion or attenuation of muscle atrophy have not been characterized at the molecular level until now. Here, we applied cDNA microarrays to investigate the transcriptional response of androgen-sensitive Levator ani muscle (LA) during atrophy reversion. Most of the differentially expressed genes behaved as atrogenes and responded to castration-induced atrophy. However, seven genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, and MKL1) did not respond to castration but instead responded exclusively to testosterone replacement. Considering that almost all proteins encoded by these genes are associated with the reversion of atrophy and may function as regulators of cell proliferation/growth, our results provide new perspectives on the existence of anti-atrogenes.

TGF-β1 and oxidative stress are involved in cancer progression, but in melanoma, their role is still controversial. Our aim was to correlate plasma TGF-β1 levels and systemic oxidative stress biomarkers in patients with melanoma, with or without disease metastasis, to understand their participation in melanoma progression. Thirty patients were recruited for melanoma surveillance, together with 30 healthy volunteers. Patients were divided into two groups: Non-metastasis, comprising patients with tumor removal and no metastatic episode for 3 years; and Metastasis, comprising patients with a metastatic episode. The plasmatic cytokines TGF-β1, IL-1 β, and TNF-α were analyzed by ELISA. For oxidative stress, the following assays were performed: malondialdehyde (MDA), advanced oxidation protein products (AOPP) levels, total radical-trapping antioxidant parameter (TRAP) and thiol in plasma, and lipid peroxidation, SOD and catalase activity and GSH in erythrocytes. Patients with a metastatic episode had less circulating TGF-β1 and increased TRAP, thiol, AOPP and lipid peroxidation levels. MDA was increased in both melanoma groups, while catalase, GSH, and IL-1β was decreased in Non-metastasis patients. Significant negative correlations were observed between TGF-β1 levels and systemic MDA, and TGF-β1 levels and systemic AOPP, while a positive correlation was observed between TGF-β1 levels and erythrocyte GSH. Lower levels of TGF-β1 were related to increased oxidative stress in Metastasis patients, reinforcing new evidence that in melanoma TGF-β1 acts as a tumor suppressor, inhibiting tumor relapse. These findings provide new knowledge concerning this cancer pathophysiology, extending the possibilities of investigating new therapies based on this evidence.

The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr). A life span experiment was conducted as the third experiment. Creatine was supplied in drinking water for 21 days (8 g/L) in all cases. Tumor implantation consisted of a suspension of Walker-256 cells (8.0 × 10(7) cells in 0.5 mL of PBS). The progressive increase (P

The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 μM) and experimental concentrations of metformin (1000 and 5000 μM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor β1 (TGF-β1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-β1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer.

Background Cachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L-glutamine 2% may have beneficial effects in cancer-related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied. Methods Twenty-eight male Wistar rats were divided into four groups: control (C), control supplemented with L-glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L-glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis. Key Results Tumor-bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor-bearing rats compared to controls. L-glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L-glutamine reduced the size of tumors and also tumor-induced cachexia that was not due to altered food intake. Conclusions & Inferences There are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L-glutamine has differential and complex effects of ICC, it reduces tumor size and tumor-associated cachexia, which supports its beneficial therapeutic role in cancer.

The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema.

Calsequestrin-1 knockout (CASQ1-null) mice suffer lethal episodes when exposed to strenuous exercise and environmental heat, crises known as exertional/environmental heatstroke (EHS). We previously demonstrated that administration of exogenous antioxidants (N-acetylcysteine and trolox) reduces CASQ1-null mortality during exposure to heat. As aerobic training is known to boost endogenous antioxidant protection, we subjected CASQ1-null mice to treadmill running for 2 months at 60% of their maximal speed for 1 h, 5 times/week. When exposed to heat stress protocol (41°C/1 h), the mortality rate of CASQ1-null mice was significantly reduced compared to untrained animals (86% versus 16%). Protection from heatstrokes was accompanied by a reduced increase in core temperature during the stress protocol and by an increased threshold of response to caffeine of isolatedextensor digitorum longusmuscles duringin vitrocontracture test. At cellular and molecular levels, aerobic training (i) improved mitochondrial function while reducing their damage and (ii) lowered calpain activity and lipid peroxidation in membranes isolated from sarcoplasmic reticulum and mitochondria. Based on this evidence, we hypothesize that the protective effect of aerobic training is essentially mediated by a reduction in oxidative stress during exposure of CASQ1-null mice to adverse environmental conditions.

In cancer cachexia, the role of nitric oxide (NO) in the central nervous system remains unclear. Cerebellar degeneration has been reported in cancer patients, but the participation of NO has not been studied. Thus, this study investigated the mechanism of oxidative cerebellar injury in a time-course cancer cachexia experimental model. The cachexia index is progressive and evident during the evolution of the tumor. Nitric oxide and lipid hydroperoxidation quantification was performed using a very sensitive and precise chemiluminescence method, which showed that both analyzed parameters were increased after tumor implantation. In the day 5 group, NO was significantly increased, and this experimental time was chosen to treat the rats with the NO inhibitors N-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). When treated with NO inhibitors, a significant decrease in both NO and lipid hydroperoxide levels occurred in the cerebellum. 3-nitrotyrosine was also analyzed in cerebellar tissue by immunohistochemistry; it was increased at the three experimental time points studied, and decreased when treated with L-NAME and AG. Besides demonstrating that lipid hydroperoxidation in the cerebellum of rats with cachexia increases in a time-dependent manner, this study is the first to describe the participation of NO and its oxidized product 3-NT in the cerebellum of cachectic rats bearing the Walker 256 solid tumor.

The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers, and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n = 9), tumor-bearing (n = 9), exercised (n = 9), and tumor-bearing exercised (n = 10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails for 6 weeks. The physical activity of control and tumor-bearing rats was confined to the space of the cage. After this period, tumor-bearing and tumor-bearing exercised animals were inoculated subcutaneously with Walker-256 tumor cells (11.0 × 107 cells in 0.5 mL of phosphate-buffered saline) while control and exercised rats were injected with vehicle. Following inoculation, rats maintained resistance exercise training (exercised and tumor-bearing exercised) or sedentary behavior (control and tumor-bearing) for 12 more days, after which they were euthanized. Results showed muscle wasting in the tumor-bearing group, with body weight loss, increased systemic leukocytes, and inflammatory interleukins as well as muscular oxidative stress and reduced mTOR signaling. In contrast, RET in the tumor-bearing exercised group was able to mitigate the reduced body weight and muscle wasting with the attenuation of muscle oxidative stress and systemic inflammatory markers. RET also prevented loss of muscle strength associated with tumor development. RET, however, did not prevent the muscle proteolysis signaling via FBXO32 gene messenger RNA expression in the tumor-bearing group. In conclusion, RET performed prior tumor implantation prevents cachexia development by attenuating tumor-induced systemic pro-inflammatory condition with muscle oxidative stress and muscle damage.

SummaryIntroductionSmoking cessation promotes health benefits and, despite cigarette smoking be an important pro inflammatory stimulus, there are few studies concerning the nasal and systemic inflammation; as well as the mucociliary clearance behavior in smokers after short period of smoking cessation.AimTo evaluate the nasal and systemic inflammatory markers and mucociliary clearance behavior after 30 days of cigarette smoking abstinence.MethodsTwenty-five smokers were included and divided into two groups: abstinent smokers (n = 14) and current smokers (n = 11). Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10 were measured on nasal lavage and blood serum samples by ELISA at baseline and after 30 days. The mucociliary clearance, exhaled carbon monoxide (exCO) and carboxyhemoglobin (HbCO) were also measured at the same moments.ResultsThere was a decrease of TNF-α level only in blood serum at 30 days of abstinence compared to current smokers. The mucociliary clearance improved and there was a reduction in exCO and HbCO (p

Objective: To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity, muscle strength, fat-free mass, and systemic inflammation in patients with chronic obstructive pulmonary disease. Design: A prospective, randomized, eight-week clinical trial. Setting: The study was conducted in a university-based, outpatient, physical therapy clinic. Subjects: A total of 49 patients with moderate chronic obstructive pulmonary disease. Interventions: Participants were randomly assigned to perform elastic tubing training or conventional resistance training three times per week for eight weeks. Main measures: The primary outcome measure was functional exercise capacity. The secondary outcome measures were peripheral muscle strength, health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire (CRDQ), fat-free mass, and cytokine profile. Results: After eight weeks, the mean distance covered during six minutes increased by 73 meters (±69) in the elastic tubing group and by 42 meters (±59) in the conventional group ( p < 0.05). The muscle strength and quality of life improved in both groups ( P < 0.05), with no significant differences between the groups. There was a trend toward an improved fat-free mass in both groups ( P = 0.05). After the first and last sessions, there was an increase in interleukin 1β (IL-1β) and interleukin 10 (IL-10) in both groups, while tumour necrosis factor alpha (TNF-α) was stimulated only in the conventional training group. Conclusion: Elastic tubing training had a greater effect on functional exercise capacity than conventional resistance training. Both interventions were equally effective in improving muscle strength and quality of life.

Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20mg/mL, E20 and 40mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68±392.44URL/g tissue to 4696.63±1076.70URL/g tissue, p

Central core disease (CCD) is a congenital myopathy linked to mutations in the ryanodine receptor type 1 (RYR1), the sarcoplasmic reticulum Ca2+release channel of skeletal muscle. CCD is characterized by formation of amorphouscoreswithin muscle fibers, lacking mitochondrial activity. In skeletal muscle of RYR1Y522S/WTknock-in mice, carrying a human mutation in RYR1 linked to malignant hyperthermia (MH) withcores, oxidative stress is elevated and fibers present severe mitochondrial damage andcores. We treated RYR1Y522S/WTmice with N-acetylcysteine (NAC), an antioxidant providedad libitumin drinking water for either 2 or 6 months. Our results show that 2 months of NAC treatment starting at 2 months of age, when mitochondrial and fiber damage was still minimal, (i) reduce formation ofunstructuredandcontracture cores, (ii) improve muscle function, and (iii) decrease mitochondrial damage. The beneficial effect of NAC treatment is also evident following 6 months of treatment starting at 4 months of age, when structural damage was at an advanced stage. NAC exerts its protective effect likely by lowering oxidative stress, as supported by the reduction of 3-NT and SOD2 levels. This work suggests that NAC administration is beneficial to prevent mitochondrial damage and formation ofcoresand improve muscle function in RYR1Y522S/WTmice.

Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress.

This study aimed to evaluate the intestinal mucosa of the duodenum and jejunum of Walker-256 tumor-bearing rats supplemented with l-glutamine. Thirty-two male 50-day-old Wistar rats (Rattus norvegicus) were randomly divided into four groups: control (C), control supplemented with 2 % l-glutamine (GC), Walker-256 tumor (WT), and Walker-256 tumor supplemented with 2 % l-glutamine (TWG). Walker-256 tumor was induced by inoculation viable tumor cells in the right rear flank. After 10 days, celiotomy was performed and duodenal and jejunal tissues were removed and processed. We evaluated the cachexia index, proliferation index, villus height, crypt depth, total height of the intestinal wall, and number of goblet cells by the technique of periodic acid-Schiff (PAS). Induction of Walker-256 tumor promoted a reduction of metaphase index in the TW group animals, which was accompanied by a reduction in the villous height and crypt depths, resulting in atrophy of the intestinal wall as well as increased PAS-positive goblet cells. Supplementation with l-glutamine reduced the tumor growth and inhibited the development of the cachectic syndrome in animals of the TWG group. Furthermore, amino acid supplementation promoted beneficial effects on the intestinal mucosa in the TWG animals through restoration of the number of PAS-positive goblet cells. Therefore, supplementation with 2 % l-glutamine exhibited a promising role in the prevention of tumor growth and cancer-associated cachexia as well as restoring the intestinal mucosa in the duodenum and jejunum of Walker-256 tumor-bearing rats.

INTRODUÇÃO: A prática de exercício físico proporciona aumento da produção de espécies reativas de oxigênio (ERO) resultantes do metabolismo aeróbio e, gera uma quantidade significativa de calor, em conseqüência da produção de energia, resultando em sobrecarga orgânica. A associação entre ERO e exercício, e entre exercício e variações da temperatura ambiente têm sido estudadas, contudo, há escassez de informações que considere a associação entre produção de radicais livres no miocárdio e atividade física em temperatura elevada. OBJETIVO: Comparar a produção de ERO em miocárdio de ratos submetidos ao treinamento de baixa intensidade em diferentes temperaturas. MÉTODOS: Foram utilizados 20 ratos Wistar, machos, jovens, peso (250 a 280g), divididos em quatro grupos: G1 (n = 5) expostos ao treinamento e calor (39º ± 1C); G2 (n = 5) expostos somente ao calor durante o mesmo período de G1, sem treinamento; G3 (n = 5) expostos ao treinamento em temperatura ambiente (22º ± 1C); G4 (n = 5) expostos à temperatura ambiente sem treinamento. O treinamento foi realizado em esteira rolante climatizada por cinco semanas, evoluindo 5 minutos a cada duas sessões finalizando em 60 minutos em baixa intensidade 8m/min. O ambiente foi controlado entre 39 ± 1ºC e 22 ± 1ºC e entre 40 e 60 % de umidade relativa. A lipoperoxidação foi avaliada por Quimiluminescência (QL). A análise dos dados foi realizada a partir do teste Two Way ANOVA para análise da QL e t de student para a Capacidade Antioxidante Total (TRAP). RESULTADOS: A análise da QL revelou uma curva de emissão de luz significantemente mais baixa para o grupo exposto ao exercício em normotermia comparado aos sedentários mantidos no calor. A análise da TRAP mostrou diminuição em todos os grupos experimentais em relação ao G4. CONCLUSÃO: Concluiu-se que houve níveis menores de produção de ERO nos grupos submetidos somente ao calor ou somente ao exercício.INTRODUCTION: The practice of physical exercise causes increase in production of oxygen reactive species (ORS), derived from the aerobic metabolism, creating a significant amount of heat due to the energy production resulting in organic overload. The associations between ORS and exercise, as well as exercise and air temperature variations have been studied; however there is a lack of information on the scientific literature concerning the association between the myocardium free radicals production and physical activity under high temperature. OBJECTIVE: The goal of this study was to compare the myocardium ORS production in rats submitted to low intensity training at different temperatures. METHODOLOGY: Twenty Wistar young male rats, with weight rage from 250 and 280 grams were used. They were divided in four groups: (G1 n = 5) exposed to training and heat (39 ± 1°C); (G2 n = 5) exposed to heat without training; (G3 n = 5) exposed to training and air temperature (22 ± 1°C); (G4 n = 5) exposed to air temperature without training. The training was performed on a treadmill in a controlled temperature room during 5 weeks, increasing 5 minutes every two sessions, reaching a total of 60 minutes under low intensity effort, 8 m/min. Room temperature was controlled between 39 ± 1° and 22 ± 1°, as well as between 40 to 60% of relative humidity. Lipoperoxidase was evaluated by Chemiluminescense (QL). Data analysis was accomplished using Two-Way ANOVA test. RESULTS: The QL analysis results revealed a light emission curve significantly lower for the animals exposed to room temperature exercise, compared to the sedentary ones kept under heat. TRAP analysis has showed a decrease in every experimental group in relation to G4. CONCLUSION: It can be concluded that there were lower levels of ORS production in the groups submitted either to heat only or exercise only.

This study highlights the systemic oxidative changes in patients submitted to primary cutaneous melanoma removal. Cutaneous melanoma is highly aggressive and its incidence is increasing worldwide. We evaluated systemic oxidative stress (OS) and 3-nitrotyrosine (3-NT) expression in melanoma tissue in relation to the Breslow thickness in patients under surveillance. Forty-three patients with cutaneous melanoma and 50 healthy volunteers were recruited. Patients were divided into two groups according to the tumor's Breslow thickness: T1/T2 (

We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor–bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed. Protein expression levels of key enzymes of gluconeogenesis, that is, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, were analyzed by western blot and immunohistochemical techniques. In addition, plasma corticosterone, glucose, insulin, and urea levels were evaluated. The WTG group showed significantly increased plasma glucose and insulin levels ( p < 0.05); however, plasma corticosterone and urea remained unchanged. Moreover, the WTG group showed increased immunoreactive staining for jejunal phosphoenolpyruvate carboxykinase and increased expression of duodenal glucose-6-phosphatase. Furthermore, the WTG group presented with less intense cancer cachexia and slower tumor growth. These results could be attributed, at least partly, to increased intestinal gluconeogenesis and insulinemia, and better glycemia maintenance during fasting in Walker-256 tumor rats on a diet supplemented with l-glutamine.

Cardiac cachexia is a syndrome that has received increased attention in recent years. Although an association between proteolysis and cardiac cachexia has been proposed, the direct influence of oxidative stress on the process has not been demonstrated. In the present study, the right (RH) and left (LH) hearts (atrium and ventricle of each side of the heart) were collected from rats at the 5th and 10th days after phosphate buffer (control) orWalker-256 solid tumour implantation. Immediately after sacrifice, cachexia was determined in tumour-bearing animals by the formula: [(inicial body weight-final body weight+tumour weight+weight gain of control group)/(initial body weight+body mass gain of control group)]×100%; RH and LH were stored until use. Oxidative stress and proteolysis were determined in each collected sample. In addition, heart samples were collected from a separate set of animals to determine the thickness of the left and right ventricles. Cachexia values increased over time after tumour implantation from 6.85% at the 5th day to 17.76% at the 10th day. There was no significant difference in LH wet weight and ventricle thickness compared with the control, where as RH wet weight (0.109±0.09g at the 5th day and 0.093±0.09g at the 10th day) and thickness (420±16μm at the 5th day and 279±08μm at the 10th day) were significantly decreased at both time points when compared with control values (0.153±0.06g and 607±21μm, respectively). tert-Butyl-stimulated chemiluminescence analysis revealed a significant increase in the LH and decrease in the RH oxidative stress profiles. Carbonylated proteins increased in the LH (140%, p0.05) and RH (100%, p0.05) at the 5th day, and significantly decreased in both sides on the 10th day compared to controls. Chemotrypsin-like, caspase-like, and calpain-like activities were evaluated by chemiluminescence, and only calpain-like activity was found to increase at the 5th day in the RH. In the LH, all proteolytic activities systems were decreased when compared with controls. Together, these results demonstrate that oxidative stress appears to play a different role in mass modulation on the LH and RH. The proteolytic systems evaluated herein also appear to have different effects on the responses developed during cardiac cachexia in the two sides of the heart.

Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = −0.95), TBARS (r = −0.98), carbonyl proteins (r = −0.99), and chymotrypsin-like proteolytic activity (r = −0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

Anemia in patients with uremia undergoing hemodialysis (HD) is a complex process that is dependent on erythropoiesis associated with erythropoietin and iron availability. Published information about an extra erythrocytic factor in the data concerning HD and the underlying mechanism by which anemia occurs remain unclear. The aim of this study was to investigate the superoxide anion generation by polymorphonuclear neutrophils and red blood cell (RBC) lipid peroxidizability as well as the possible association between these parameters and anemia in patients undergoing HD. Blood was collected from 15 volunteers prior to and following HD, and hematological data showed significant anemia at both time points. RBC lipid peroxidizability and neutrophil anion superoxide production, as evaluated by kinetics analysis, revealed increased initial and maximal velocity before and after HD. Plasma malondialdehyde (MDA) and antioxidant levels in the patient group were higher than those in the control group. RBC superoxide dismutase and catalase activities did not differ between groups. There was a significant correlation between increased RBC lipid peroxidizability and superoxide anion production and anemia in patients undergoing HD. The individual variation in plasma MDA was accompanied by superoxide anion production. The RBC lipid peroxidizability, mediated by neutrophil-generated superoxide anions, seems to be a plausible mechanism for explaining, in part, the extraerythrocytic damage that leads to anemia in patients on HD.

Aims The purpose of the present work was to investigate the effect of cyclooxygenase-2 (COX-2) inhibition on the cardiovascular and inflammatory aspects promoted by monosodium glutamate (MSG)-induced obesity in rats. Main methods Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control). Treatment with celecoxib (50 mg/kg ip) or saline (0.9% NaCl ip) began at 60 days of age. At 90 days, all rats were anesthetized for catheterization of the femoral artery, and the mean arterial pressure (MAP) and heart rate (HR) were recorded once consciousness was regained. Key findings MSG obese rats were hypertensive (MAP = 138 ± 4 mm Hg) compared with controls (MAP = 118 ± 2 mm Hg). After treatment with celecoxib, the hypertension was attenuated (MAP = 126 ± 2 mm Hg) in obese rats without changes in HR. The retroperitoneal and periepididymal fat weighed more in obese rats (Obese: Retro = 7.08 ± 0.51, Peri = 6.36 ± 0.81, Control: Retro = 3.60 ± 0.46; Peri = 3.24 ± 0.42), but celecoxib did not alter these parameters. Plasma nitric oxide levels were not different between groups. However, the level of plasma prostaglandins, the immunohistochemical staining of COX-2 in cardiac tissue and plasma lipoperoxidation were higher in obese rats, and celecoxib attenuated these parameters. MSG produced liver steatosis that was also attenuated following celecoxib treatment. Significance Our data demonstrate an association between increased blood pressure and products of COX-2 in obese rats, suggesting a role for prostaglandins in the hypertensive and inflammatory aspects of MSG-induced obesity.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:41Z No. of bitstreams: 1 S1517-86922007000600011.pdf: 586749 bytes, checksum: ac53a308efd5a30e5d4ceb4873cc9720 (MD5) Made available in DSpace on 2013-08-22T18:41:41Z (GMT). No. of bitstreams: 1 S1517-86922007000600011.pdf: 586749 bytes, checksum: ac53a308efd5a30e5d4ceb4873cc9720 (MD5) Previous issue date: 2007-12-01 Made available in DSpace on 2013-09-30T18:09:56Z (GMT). No. of bitstreams: 2 S1517-86922007000600011.pdf: 586749 bytes, checksum: ac53a308efd5a30e5d4ceb4873cc9720 (MD5) S1517-86922007000600011.pdf.txt: 33827 bytes, checksum: 20bb199a4d7dd27855be08b0c9c4879b (MD5) Previous issue date: 2007-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:23:22Z No. of bitstreams: 2 S1517-86922007000600011.pdf: 586749 bytes, checksum: ac53a308efd5a30e5d4ceb4873cc9720 (MD5) S1517-86922007000600011.pdf.txt: 33827 bytes, checksum: 20bb199a4d7dd27855be08b0c9c4879b (MD5) Made available in DSpace on 2014-05-20T13:23:22Z (GMT). No. of bitstreams: 2 S1517-86922007000600011.pdf: 586749 bytes, checksum: ac53a308efd5a30e5d4ceb4873cc9720 (MD5) S1517-86922007000600011.pdf.txt: 33827 bytes, checksum: 20bb199a4d7dd27855be08b0c9c4879b (MD5) Previous issue date: 2007-12-01 Fundação para o Desenvolvimento da UNESP (FUNDUNESP) INTRODUÇÃO: A prática de exercício físico proporciona aumento da produção de espécies reativas de oxigênio (ERO) resultantes do metabolismo aeróbio e, gera uma quantidade significativa de calor, em conseqüência da produção de energia, resultando em sobrecarga orgânica. A associação entre ERO e exercício, e entre exercício e variações da temperatura ambiente têm sido estudadas, contudo, há escassez de informações que considere a associação entre produção de radicais livres no miocárdio e atividade física em temperatura elevada. OBJETIVO: Comparar a produção de ERO em miocárdio de ratos submetidos ao treinamento de baixa intensidade em diferentes temperaturas. MÉTODOS: Foram utilizados 20 ratos Wistar, machos, jovens, peso (250 a 280g), divididos em quatro grupos: G1 (n = 5) expostos ao treinamento e calor (39º ± 1C); G2 (n = 5) expostos somente ao calor durante o mesmo período de G1, sem treinamento; G3 (n = 5) expostos ao treinamento em temperatura ambiente (22º ± 1C); G4 (n = 5) expostos à temperatura ambiente sem treinamento. O treinamento foi realizado em esteira rolante climatizada por cinco semanas, evoluindo 5 minutos a cada duas sessões finalizando em 60 minutos em baixa intensidade 8m/min. O ambiente foi controlado entre 39 ± 1ºC e 22 ± 1ºC e entre 40 e 60 % de umidade relativa. A lipoperoxidação foi avaliada por Quimiluminescência (QL). A análise dos dados foi realizada a partir do teste Two Way ANOVA para análise da QL e t de student para a Capacidade Antioxidante Total (TRAP). RESULTADOS: A análise da QL revelou uma curva de emissão de luz significantemente mais baixa para o grupo exposto ao exercício em normotermia comparado aos sedentários mantidos no calor. A análise da TRAP mostrou diminuição em todos os grupos experimentais em relação ao G4. CONCLUSÃO: Concluiu-se que houve níveis menores de produção de ERO nos grupos submetidos somente ao calor ou somente ao exercício. INTRODUCTION: The practice of physical exercise causes increase in production of oxygen reactive species (ORS), derived from the aerobic metabolism, creating a significant amount of heat due to the energy production resulting in organic overload. The associations between ORS and exercise, as well as exercise and air temperature variations have been studied; however there is a lack of information on the scientific literature concerning the association between the myocardium free radicals production and physical activity under high temperature. OBJECTIVE: The goal of this study was to compare the myocardium ORS production in rats submitted to low intensity training at different temperatures. METHODOLOGY: Twenty Wistar young male rats, with weight rage from 250 and 280 grams were used. They were divided in four groups: (G1 n = 5) exposed to training and heat (39 ± 1°C); (G2 n = 5) exposed to heat without training; (G3 n = 5) exposed to training and air temperature (22 ± 1°C); (G4 n = 5) exposed to air temperature without training. The training was performed on a treadmill in a controlled temperature room during 5 weeks, increasing 5 minutes every two sessions, reaching a total of 60 minutes under low intensity effort, 8 m/min. Room temperature was controlled between 39 ± 1° and 22 ± 1°, as well as between 40 to 60% of relative humidity. Lipoperoxidase was evaluated by Chemiluminescense (QL). Data analysis was accomplished using Two-Way ANOVA test. RESULTS: The QL analysis results revealed a light emission curve significantly lower for the animals exposed to room temperature exercise, compared to the sedentary ones kept under heat. TRAP analysis has showed a decrease in every experimental group in relation to G4. CONCLUSION: It can be concluded that there were lower levels of ORS production in the groups submitted either to heat only or exercise only. UNESP FCT Departamento de Fisioterapia FAMERP Departamento de Cardiologia e Cirurgia Cardiovascular UEL Departamento de Ciências Patológicas UNESP FM Departamento de Clínica Médica FAMERP Programa de Pós-Graduação em Ciências da Saúde UNESP FCT Departamento de Fisioterapia UNESP FM Departamento de Clínica Médica

A caquexia é definida como uma síndrome de progressiva perda de peso, e persistente perda de massa magra. É característica freqüente de pacientes portadores de câncer e se caractreiza por perda maior que 10% da massa corporal total, sendo responsável por cerca de 22% dos óbitos em pacientes com doença maligna avançada. A perda maciça de massa muscular é responsável pela maior parte da perda de peso total e ocorre independentemente da ingesta alimentar ou absorção de nutrientes. Alguns grupos têm demonstrado que o estresse oxidativo moderado pode aumentar a degradação proteica através do superexpressão dos componentes da via ubiquitina-proteassoma. Entre as modificações induzidas pelas ERO, se incluem a carbonilação proteica, a peroxidação lipídica, e o consumo das defesas antioxidantes solúveis. Esse trabalho se propôs a esclarecer o envolvimento do estresse oxidativo no desenvolvimento da caquexia relacionada ao câncer, em músculo esquelético de ratos com a forma subcutânea do tumor de Walker-256. Para isso, foram utilizados ratos Wistar machos de 200-250g, com água e ração ad libitum. O primeiro grupo (n=6) recebeu inoculação subcutânea, no flanco direito, de 0,5 mL de PBS; o segundo grupo (n=18) recebeu implantação subcutânea no flanco direito de uma supensão células tumorais em 0,5 mL de PBS; e um terceiro grupo (n=6) foi inoculado com PBS e recebeu a mesma quantidade de ração previamente ingerida pelos animais inoculados com tumor, durante 14 dias. Nos dias 5, 10 e 14, após a inoculação do tumor, os animais foram pesados, decapitados, e o tumor cuidadosamente dissecado e pesado. O músculo gastrocnêmio esquerdo de cada animal foi rapidamente retirado para pesagem e armazenamento. Os músculos foram homogeneizados em tampão gelado, e submetidos às reações com o TBA, quimiluminescência estimulada por tert-butil, e quantificação das defesas antioxidantes solúveis. A implantação do tumor de Walker-256 levou à diminuição progressiva do peso corporal no 5º e 10º dias, que foi acompanhada pela progressiva perda de massa do músculo gastrocnêmio (2,9%, 12,3%, e 15,8% no 5º, 10º e 14º dias, respectivamente). Os animais que receberam a mesma quantidade de ração consumida pelos animais inoculados com o tumor apresentaram, em 14 dias, a mesma diminuição encontrada no grupo 5 dias, quando comparados ao controle (10.1 ± 1.55%). Os índices de massa muscular/massa corporal total observados foram: um aumento de 0,56 no grupo pair-fed, e diminuições de 0,27 no grupo 5º dia, 0,86 no grupo 10º dia, e 0,81 no grupo 14º dia. A lipoperoxidação, avaliada pela formação de TBARS, mostrou um aumento significativo no 10º dia, chegando a aproximadamente 2,5 vezes os valores encontrados no grupo controle. A QL estimulada por t-butil hidroperóxido mostrou aumento altamente significativo (p

O TT vírus (TTV) foi primeiramente descrito no Japão, em 1997, por T. Nishizawa, no soro de pacientes com hepatite, pós-transfusão, não-A-G. Tem sido intensivamente investigado, desde então, como uma possível adição à lista dos vírus indutores de hepatite. O TTV é um vírus DNA não-envelopado, de fita simples. Uma considerável variabilidade genética tem sido demonstrada por parte do TTV, o que tem levado pesquisadores a agrupar isolados do vírus em inúmeros genótipos e subtipos. No entanto a significância clínica da infecção por TTV permanece desconhecida. Ele é freqüentemente detectado em fluidos corporais e seu componente mais bem elucidado atualmente é o genoma. Conhecimentos relacionados ao TTV têm aumentado constantemente, porém vários aspectos fundamentais permanecem obscuros. Esta revisão apresenta algumas das propriedades moleculares do TT vírus. TT virus (TTV) was first reported in Japan in 1997 by T. Nishizawa in sera from non-A to non-G post-transfusion hepatitis patients. It has been intensively investigated, ever since, as a possible addition to the list of hepatitis-inducing viruses. The TTV is an unenveloped, single-stranded DNA virus. Considerable genetic variability of TTV has been demonstrated and has led investigators to group its isolates into numerous genotypes and subtypes. However, the clinical significance of TTV infection remains unknown. It is frequently detected in the serum and in other body fluids of humans. The component of TTV currently best understood is its genome. Knowledge related to TTV has increased rapidly, but many fundamental aspects remain unclear. This review shows some of the molecular properties of TT virus.

Made available in DSpace on 2014-12-03T13:11:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-11-21Bitstream added on 2014-12-03T13:22:30Z : No. of bitstreams: 1 WOS000328056200001.pdf: 490364 bytes, checksum: 0b894cc58983db4be19e0ed973c9f95b (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Univ Estadual Paulista, from Presidente Prudente, Brazil Background: Localized exercises are widely used in rehabilitation processes. The predominant options are exercises with an emphasis on either concentric or eccentric contractions. Eccentric exercises promote greater strength gains compared to classical concentric stimuli, but can cause muscle damage. The aim of present study was to compare strength training composed of 10 sessions with progressive loads between groups with a predominance of concentric versus eccentric contraction through an analysis of isotonic strength, pressure pain threshold, creatine kinase, tumor necrosis factor-alpha and cortisol.Methods: One hundred twenty male subjects were divided into four groups: C1 and E1 - single session of maximum strength with emphasis on concentric and eccentric contraction, respectively; C10 and E10 - 10 sessions with progressive loads from 80% to maximum strength with emphasis on concentric and eccentric contraction, respectively.Results: Isotonic strength increased by 10% in E10 following the ten training sessions. C1 and E1 exhibited a lower pressure pain threshold 48 hours after the sessions in comparison to C10 and E10, respectively. Creatine kinase was increased in C1 in comparison to baseline, with significant differences (p

As doenças inflamatórias intestinas (DII) estão entre os principais distúrbios que acometem o trato gastrointestinal, destacando-se a retocolite ulcerativa (RCU). O processo inflamatório na RCU é capaz de ativar fibras intestinais direcionadas aos gânglios de raíz dorsal (GRD), que transmite a informação ao sistema nervoso central (SNC) dando origem a dor. Em geral, no SNC, o espaço entre as células é ocupado por matriz extracelular amorfa e difusa, porém ao redor de populações neuronais específicas a matriz se torna altamente especializada, sendo chamada de Rede perineuronal (RPN). A RPN está relacionada como o desenvolvimento neuronal, sinaptogênese, plasticidade sináptica e neuroproteção.Os relatos da presença da RPN estão restritos ao SNC, não existindo estudos que avaliem sua relação com a inervação aferente extrínseca do cólon distal e com a inflamação presente na RCU. Por isso, objetivo deste estudo foi avaliar a presença da RPN na inervação espinal aferente do cólon distal, bem como a influência do processo inflamatório presente na RCU sobre esta rede. Foram utilizados 20 camundongos C57BL/6 machos distribuídos em 4 grupos (n=5): GCa: recebeu água autoclavada durante 7 dias; RCUa: receberam Dextran sulfato de sódio 3% (DSS 3%) durante 7 dias; GCc: água autoclavada durante 29 dias; RCUc: 3 ciclos de DSS 3% durante 5 dias, intercalados por 2 ciclos de 7 dias com água autoclavada. Durante o tratamento, os animais foram avaliados clinicamente. Ao fim, foram submetidos à eutanásia e coletou-se o cólon distal para análise histopatológica e os GRD de níveis espinais bilaterais L6-S1, seus respectivos nervos esplânicos, para avaliar a inervação espinal aferente do cólon distal. As secções de tecido nervoso foram submetidas à técnica de histoimunofluorescência, utilizando-se a lectina Wisteria floribunda aglutinina (WFA) e anticorpos contra o peptídeo relacionado ao gene da calcitonina (CGRP) ou contra periferina c- 19. Foram quantificados 500 corpos celulares e prolongamentos, além da mensuração dos pericários WFA+ e WFA-, além da co-marcação com CGRP nos GRD. Com auxílio de microscópio confocal, foram quantificados 30 neurônios por animal e identificados os subtipos de marcação de WFA, além do número de células gliais satélites ao seu redor. Em relação à marcação com WFA, foi possível observar a presença de RPN entorno de todas as estruturas analisadas. Também observamos que a RCU aumentou o número de neurônios WFA positivos bem como a área ocupada pelos seus corpos celulares no córtex de GRD (p

A Caquexia é uma síndrome multifatorial e complexa, presente em doenças inflamatórias crônicas, como diabetes, Doença Pulmonar Obstrutiva Crônica e câncer. É frequentemente associada ao declínio da função física e qualidade de vida, baixa tolerância às terapias, e à diminuição da sobrevida. No câncer, é a causa direta da mortalidade em até 40% dos pacientes. Diversos fenômenos estão envolvidos na fisiopatologia da caquexia, dentre eles fenômenos metabólicos, inflamatórios e oxidativos. Sabe-se que a produção de citocinas pró-inflamatórias está relacionada com diminuição da ingestão alimentar, bem como com a formação de espécies reativas de oxigênio que regulam positivamente vias de degradação proteica e atrofia muscular. O objetivo deste estudo foi diferenciar os efeitos da caquexia em diferentes tipos de fibras musculares esqueléticas, em tempos experimentais distintos, bem como o envolvimento de alterações bioquímicas, oxidativas e funcionais em um modelo experimental de carcinoma colorretal - C26 em camundongos. Foram coletados os músculos sóleo, extensor longo dos dedos, gastrocnêmio e tibial anterior para análise da perda de massa muscular. Modificações oxidativas e lipídeos foram avaliadas por meio da quantificação de malondialdeído por TBARS e quimiluminescência estimulada por butil hidroperóxido, a oxidação de proteínas por ELISA, e western blotting foi a técnica escolhida para quantificação da proteína Retículo Sarcoplasmático Cálcio ATPase. Nossos resultados apontam para perda de massa muscular oxidativa no estágio de caquexia, que foram coincidentes com os achados da carbonilação de proteínas, enquanto a análise de fibras mistas demonstrou lesão oxidativa de membranas nos estágios inicial e tardio da síndrome. A avaliação de parâmetros funcionais de mobilidade e capacidade física mostrou que o comprometimento funcional atinge diferentes habilidades durante os estágios de desenvolvimento da caquexia, apontando para correlação nos distúrbios do cálcio. Este trabalho sugere que, neste modelo experimental, diferentes tipos de fibras musculares respondem de maneiras diferentes, e que o comprometimento funcional também varia temporalmente, abrindo possibilidades para tratamento específico durante os diferentes estágios da síndrome. Cachexia is a multifactorial and complex syndrome present in chronic inflammatory diseases such as diabetes, Chronic Obstructive Pulmonary Disease and cancer. It is often associated with declining in physical function and quality of life, poor tolerance to therapies, and decreased survival. In cancer, it is the direct cause of mortality in up to 40% of patients. Several phenomena are involved in the pathophysiology of cachexia, including metabolic, inflammatory, and oxidative stress. It is known that the production of pro-inflammatory cytokines is related to decreased food intake, as well as the formation of reactive oxygen species that positively regulate protein degradation pathways and muscle atrophy. The aim of this study was to differentiate the effects of cachexia in different types of skeletal muscle fibers, at different experimental times, as well as the involvement of biochemical, oxidative, and functional alterations in an experimental model of colorectal carcinoma - C26 in mice. The soleus, extensor digitorum longus, gastrocnemius and tibialis anterior muscles were collected to analyze the loss of muscle mass. Oxidative to lipid were evaluated through the quantification of Malondialdehyde by TBARS and chemiluminescence stimulated by butyl hydroperoxide, protein oxidation by ELISA, and western blotting was the chosen technique for quantification of the Sarcoplasmic Reticulum Calcium ATPase protein. Our results point to loss of oxidative muscle mass in the cachexia stage, which coincided with the findings of protein carbonylation, while the mixed fiber analysis showed oxidative damage to membranes in the early and late stages of the syndrome. The evaluation of functional parameters of mobility and physical capacity showed that functional impairment affects different abilities at different stages of cachexia development, pointing to a correlation in calcium disorders. This work suggests that, in this experimental model, different types of muscle fibers respond in different ways, and that functional impairment also varies over time, opening possibilities for treating the syndrome.

O carcinoma de tireoide é considerado o tipo mais comum de câncer endócrino e uma das neoplasias que mais cresce em número de diagnósticos. A incidência aumenta a cada ano, sendo o carcinoma papilífero de tireoide (CPT) o tipo mais prevalente. A K1, diferentemente de outras linhagens, possui uma mutação em BRAF (V600E), que representa grande parte dos casos de CPT, e proteína p53 ativa, culminando numa linhagem única de carcinoma tireoidiano. A linhagem de células de CPT- K1, é uma das linhagens que possui o menor número de estudos que discutem sua interação com espécies reativas (ER), pouco sabendo-se sobre ela nesse cenário. O efeito das ER em células tumorais pode desempenhar papel tanto pró quanto anti-tumoral, justificando a necessidade de investigar o comportamento de carcinomas frente às espécies reativas. Este trabalho teve como objetivo compreender os efeitos do tratamento indireto com plasma frio atmosférico de argônio, um gerador de ER mistas, na K1. Este plasma físico é um potente produtor de ER, principalmente peróxido de hidrogênio e espécies reativas de nitrogênio (ERN). Foi avaliado o comportamento da K1 com a terapia indireta com plasma e com cada uma dessas espécies por meio da caracterização tanto da viabilidade quanto do balanço redox das células de CPT. Os tempos de irradiação (30, 60 e 120 segundos) com o plasma frio atmosférico, afetaram a K1 de forma a diminuir sua viabilidade, principalmente o tempo de 120 segundos (p

O treinamento resistido (TR) é um clássico regulador anabólico, em que a ativação do eixo Akt/mTOR é um dos mecanismos mais conhecidos na hipertrofia muscular. Contudo, ainda é desconhecida a contribuição desse eixo na atrofia muscular. O objetivo desse estudo foi investigar a contribuição da via de sinalização Akt/mTOR na atenuação da atrofia muscular esquelética induzida pelo TR em ratos inoculados com tumor de Walker-256. Experimento 1: 37 ratos foram divididos nos seguintes grupos, controle (C, n=9), tumor (T, n=9), exercitados (E, n=9) e tumor-exercitados (TE, n=10). Os animais dos grupos T e TE foram inoculados com células de Walker-256 (4x107 em 500μl de solução salina (PBS) s.c no flanco direito) e os grupos C e E inoculados com 500μl de PBS. Os grupos E e TE realizaram o protocolo de TR com cargas progressivas durante 4 semanas. Experimento 2: 30 ratos foram divididos nos seguintes grupos, controle (C, n= 6), controle tratado com rapamicina (R, n=7), tumorexercitado (TE, n=8) e tumor-exercitado tratado com Rapamicina (TER, n=9). Os animais receberam rapamicina diariamente via gavagem (1mg/kg/dia em 200μl de água) ou placebo (200μl de água). Durante 4 semanas o tumor cresceu progressivamente representando 7±2% do peso corporal dos animais. O tumor reduziu o ganho de peso corporal (-9,85%), promoveu anorexia (-32,3%) e atrofia do músculo FHL (P75=-24%) favorecendo a diminuição da força muscular (-11.09%) em relação ao grupo C. Embora o crescimento do tumor não tenha modificado a expressão de RNAm de mTOR, resultou em menores níveis de expressão da proteína-chave P70S6K (-26,4%) e p-P70S6K (-33,7%) em relação ao C. Entretanto, o TR atenuou a anorexia (+22,18%), porém, não melhorou o ganho de peso corporal (+6,35%) em relação ao grupo T. Além disso, o TR promoveu maior expressão da proteína P70S6K (+141%) e da p-P70S6K (+165,1%). Porém, não houve diferença na razão P70S6K/p-P70S6K (+1,13%) em relação ao grupo T. Adicionalmente, o tratamento com Rapamicina combinado com TR atenuou a atrofia no músculo FHL (P75=+9,29) independentemente da via Akt/mTOR. O tumor promoveu maiores concentrações de leucócitos circulantes (+150%), monócitos (+185,6%), TNF-a (+238%), IL-6 (+422%), TBARS (+135%), AOPP (+656%), RNAm de FBXO-32 (+204%), expressão de MAFbx/atrogin-1 (+308%) e MuRF-1 (+388%) comparado com o C. Por outro lado, o TR resultou em menores concentrações de leucócitos circulantes (-37%), monócitos (-46,5%), TNF-a (-60,5%), IL-6 (-71,3%), AOPP (-81,2%), maiores níveis circulantes de IL-10 (+224%) e a razão IL-10/ TNF-a (+78%) em relação ao grupo T. Além disso, o TR resultou em menor expressão da proteína atrogin-1 (-43,2%) com relação ao grupo T. Portanto, a via de sinalização Akt/mTOR pouco contribui para atenuação da atrofia do músculo FHL induzida pelo protocolo de TR em ratos inoculados com tumor de walker-256. A diminuição da degradação proteica via ativação de alvos chave do sistema ubiquitina proteassoma paralelamente à redução de citocinas pró-inflamatórias circulantes e dano oxidativo no músculo esquelético foram mais determinantes para atenuar a atrofia muscular. Resistance training (RT) is a classic anabolic regulator, in which Akt/mTOR pathway is one of the well-known mechanisms in muscular hypertrophy. However, the contribution of Akt/mTOR pathway in muscle atrophy is unkown. Therefore, the purpose of this study was to investigate the Akt/mTOR signaling pathway contribution on attenuation of muscle atrophy induced by RT in Walker-256 tumor-bearing rats. This study was conducted in two experiments. Experiment 1: 37 rats were allocated in follwing groups, control (C, n=9), tumor-bearing (T, n=9), exercised (E, n=9) and tumorbearing exercised (TE, n=10). The rats from T and TE group were inoculated with Walker-256 tumor cells (4x107 in 500μl phosphate buffer saline (PBS) s.c in flank) and rats from C and E were inoculated with vehicle (500μl PBS). Rats from E and TE peformed the RT procotol in wich consisted in climbing carring progressive loads during four weeks. Experiment 2: 30 rats were allocated in following groups, treated with rapamycin (R, n=7) and tumor-bearing treated with rapamycin exercised (TER, n=9). The rats were treated with rapamycin daily via gavage (1mg/kg/day in 200μl water) or placebo (200μl water). Over four-weeks the tumor progressively grew representing 7±2% of rat’s body weight. The tumor reduced the body weight gain (-9.85%), promoted anorexia (-32.3%) and FHL muscle atrophy (P75= -24%) favoring muscular strength loss (-11.09%) in relation C group. Although tumor growth has not modified the RNAm of mTOR, there was lower expressionn of protein-key P70S6K (+141%) and p-P70S6K (+165,1%) in relation C group. On the other hand, RT attenuated the anorexia (+22.18%), however, did not improve the body weight gain (+6.35%) in relation T group. Besides, RT promoted higher expression of protein-key P70S6K (+141%) and p-P70S6K (+165,1%). But, there was not difference in P70S6K/p-P70S6K ratio (+1.13%) in relation T group. In addition, the Rapamycin treatment combined with RT protocol attenuated the FHL muscle atrophy independently of Akt/mTOR pathway (P75=+9.29). The tumor promoted higher concentration of circulating leukocytes (+150%), percentage of monocytes (+185.6%), TNF-a (+238%), IL-6 (+422%), TBARS (+135%), AOPP (+656%), mRNA of FBXO-32 (+204%), atrogin-1 protein expression (+308%), MuRF-1 protein expression (+388%) in relation C group. Differently, RT protocol resulted in lower circulating leukocytes concentration (-37%), percentage of monocytes (-46.5%), TNF-a (-60.5%), IL-6 (-71.3%), AOPP (-81.2%), promoted higher IL-10 concentration (+224%) and IL-10/TNF-a ratio (+78%) in relation T group. Furtheremore, RT resulted in lower MAFbx/atrogin-1 protein expression (-43%) compared with C group. Therefore, the Akt/ mTOR signaling pathway little contributes to attenuation of FHL muscle atrophy induced by RT protocol in rats inoculated with walker-256 tumor. Decreased protein degradation via activation of key-targets of the proteasome ubiquitin system in parallel with the reduction of sistemic proinflammatory cytokines and oxidative damage in skeletal muscle were more determinant to attenuate muscle atrophy.