Sulfasalazine exposure during pregnancy and lactation: reproductive outcomes in male rat offspring.

CONTEXT: Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS crosses the placenta and passes into maternal milk, the consequences of maternal SAS exposure on the reproductive development of male offspring needs further study. AIMS: The current study evaluated whether maternal SAS exposure interferes with the reproductive development of male rat offspring in the neonatal, infant, pubertal and adulthood periods. METHODS: Pregnant Wistar rats (n =10/group) received 300mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21, and 3mg/kg/day of folic acid during gestation. The control group received CMC. KEY RESULTS: During puberty, maternal SAS exposure increased the total length of seminiferous tubules, and round cells were observed in the lumen of caput and cauda epididymis. Moreover, SAS induced oxidative stress-related alterations in the testes of infant and adolescent rats. CONCLUSIONS: Although maternal SAS treatment caused reproductive alterations in infant and adolescent male rats, in adulthood, there were no impairments in sperm parameters that could compromise fertility. IMPLICATIONS: This study investigated the consequences of maternal exposure to SAS on the reproductive development of male rat offspring from birth to adulthood, employing a human-relevant dose. Thus, this study provides information for better understanding of SAS treatment during critical periods of development.

Oral administration of botryosphaeran [(1 → 3)(1 → 6)-ß-d-glucan] reduces inflammation through modulation of leukocytes and has limited effect on inflammatory nociception.

Several biological activities of the fungal exopolysaccharide (1 → 3)(1 → 6)-ß-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal ß-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal ß-glucan a new possibility for complementary treating acute and chronic inflammation.

High-Fat Diet Impairs Muscle Function and Increases the Risk of Environmental Heatstroke in Mice.

Environmental heat-stroke (HS) is a life-threatening response often triggered by hot and humid weather. Several lines of evidence indicate that HS is caused by excessive heat production in skeletal muscle, which in turn is the result of abnormal Ca2+ leak from the sarcoplasmic reticulum (SR) and excessive production of oxidative species of oxygen and nitrogen. As a high fat diet is known to increase oxidative stress, the objective of the present study was to investigate the effects of 3 months of high-fat diet (HFD) on the HS susceptibility of wild type (WT) mice. HS susceptibility was tested in an environmental chamber where 4 months old WT mice were exposed to heat stress (41 °C for 1 h). In comparison with mice fed with a regular diet, mice fed with HFD showed: (a) increased body weight and accumulation of adipose tissue; (b) elevated oxidative stress in skeletal muscles; (c) increased heat generation and oxygen consumption during exposure to heat stress; and finally, (d) enhanced sensitivity to both temperature and caffeine of isolated muscles during in-vitro contracture test. These data (a) suggest that HFD predisposes WT mice to heat stress and (b) could have implications for guidelines regarding food intake during periods of intense environmental heat.

Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling.

PURPOSE: The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats. METHODS: Wistar rats were randomly assigned into three groups (n = 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals' weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin-proteasome pathways were also evaluated using real-time PCR and immunoblotting. RESULTS: The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy. CONCLUSION: Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.

Sleep restriction during peripuberty unbalances sexual hormones and testicular cytokines in rats.

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-1ß, 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.

Muscle activity prevents the uncoupling of mitochondria from Ca2+ Release Units induced by ageing and disuse.

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.

Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy.

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.

Effect of Cold Water Immersion Performed on Successive Days on Physical Performance, Muscle Damage, and Inflammatory, Hormonal, and Oxidative Stress Markers in Volleyball Players.

de Freitas, VH, Ramos, SP, Bara-Filho, MG, Freitas, DGS, Coimbra, DR, Cecchini, R, Guarnier, FA, and Nakamura, FY. Effect of cold water immersion performed on successive days on physical performance, muscle damage, and inflammatory, hormonal, and oxidative stress markers in volleyball players. J Strength Cond Res 33(2): 502-513, 2019-The aim of this study was to investigate the effects of daily cold water immersion (CWI) on physical performance, muscle damage, and inflammatory, hormonal, and oxidative stress markers in volleyball. Six players were submitted to CWI and six players to a placebo, during 5 training days. Thigh circumference, squat jump, and agility were measured on the first, third, and sixth days. On the first and sixth days, blood and saliva were collected for analysis of oxidative stress, muscle damage, and inflammatory and hormonal levels. Muscle soreness and countermovement jump were quantified daily. The physical performance comparisons did not present differences and the only between group comparison with a large effect size (ES = -1.39) was in Δ% between day 1 and day 2 for countermovement jump. Delayed onset muscle soreness and creatine kinase increased in both groups and the ESs of between group comparisons of Δ% between moments were not more than moderate. Thigh circumference increased only in the placebo group (p = 0.04) and the ES of the between group comparisons of Δ% between moments was large (1.53). No differences were found in oxidative stress, or inflammatory markers. Cortisol decreased only in the CWI-group (p ≤ 0.05) and the ESs of the between group comparisons of Δ% between moments of the testosterone to cortisol ratio (-1.94) and insulin-like growth-1 (-1.34) were large. Despite the positive effects of daily CWI on muscle edema and hormonal status, the limited effects of CWI on performance, muscle damage, inflammation markers, and reactive oxygen species mediators signal the unimportance of the daily practice of this recovery method in volleyball players.

Isoflavin-ß modifies muscle oxidative stress and prevents a thyrotoxicosis-induced loss of muscle mass in rats.

INTRODUCTION: We sought to verify whether isoflavin-beta (Iso-ß), a mixture of isoflavones with antioxidant properties, could prevent thyrotoxicosis-induced loss of muscle mass and the participation of oxidative stress (OS) in the mechanisms of this prevention. METHODS: Two experimental periods of thyrotoxicosis induction were used in Wistar rats: 3 and 5 days to assess Iso-ß effects before and after thyrotoxicosis-induced muscle wasting. After euthanasia, peritoneal fat and gastrocnemius muscle were collected, weighed, and muscle OS was assessed. RESULTS: Iso-ß prevented the loss of gastrocnemius mass in thyrotoxic rats through the prevention of muscle OS generation during thyrotoxicosis, increasing muscle total antioxidant capacity and decreasing mitochondrial cytochrome c oxidase activity, lipid peroxidation, and protein carbonyl content. CONCLUSION: Iso-ß decreased oxidative modification of proteins, which is known to exert a major role during proteolysis induction and is present in thyrotoxic myopathy, highlighting the potential action of Iso-ß in this complication of the disease. Muscle Nerve 56: 975-981, 2017.

Low doses of bisphenol A can impair postnatal testicular development directly, without affecting hormonal or oxidative stress levels.

Bisphenol A (BPA) is considered a potent endocrine disruptor, causing changes in the endocrine system due to its oestrogenic activity. Male individuals may be susceptible to endocrine, morphological and physiological alterations during testicular postnatal development. The aim of the present study was to evaluate whether exposure to BPA during the peripubertal period can damage testicular development. To this end, male Wistar rats were treated with BPA via gavage at doses of 20 or 200µgkg-1 on Postnatal Days (PND) 36-66. The control group was treated with Oil+DMSO under the same conditions. On PND 67, rats were killed. The blood was collected for hormonal analysis, the testis for sperm count, oxidative stress, histopathological and immunohistochemical analyses for ki-67 and sperm of the vas deferens for morphological analysis. Both doses of BPA resulted in abnormal sperm morphology and seminiferous tubules, with the highest dose increasing the height of the germinal epithelium and reducing the number of spermatozoa at Stages IX-XIII of spermatogenesis. In conclusion, both doses of BPA administered during the peripubertal period impaired testicular development without any effects on hormone levels (luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone levels) or oxidative stress.

Sleep restriction in Wistar rats impairs epididymal postnatal development and sperm motility in association with oxidative stress.

Good sleep quality has a direct effect on the activity of the neuroendocrine-reproductive control axis and oxidative stress. Thus, the aim of the present study was to evaluate whether sleep restriction (SR) during the peripubertal period impaired the postnatal development of the epididymis in Wistar rats. After 21 days SR (18h per day), epididymides were collected on Postnatal Day (PND) 62 for evaluation of oxidative stress markers, inflammatory profile, sperm count and histopathological and stereological analyses; in addition, the motility of spermatozoa from the vas deferens was examined. SR significantly increased lipid peroxidation and glutathione levels in the caput and cauda epididymidis, and increased levels of total radical-trapping antioxidant potential in the caput epididymidis only. Neutrophil migration to the caput or corpus epididymidis was decreased by SR, and the size of the luminal compartment in the 2A region and the epithelial compartment in the 5A/B region was also decreased. In these regions, there was an increase in the size of the interstitial compartment. The percentage of immotile spermatozoa was higher in the SR group. In conclusion, SR affects epididymal postnatal development, as well as sperm motility, in association with increased oxidative stress and a decrease in the size of the epithelial compartment in the cauda epididymidis.

Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

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.

Strength gain through eccentric isotonic training without changes in clinical signs or blood markers.

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 ≤ 0.05) in comparison to E1 at 48 and 96 hours as well as C10 at 48, 72 and 96 hours. No significant differences were found in TNF-α or cortisol among the groups or evaluation times. CONCLUSION: Eccentric contraction training promotes functional adaptation. Moreover, both concentric and eccentric contraction training have a protective effect on the muscle in relation to a single session of maximum strength exercise. TRIAL REGISTRATION: RBR-75scwh.

Oxygen Consumption and Basal Metabolic Rate as Markers of Susceptibility to Malignant Hyperthermia and Heat Stroke.

Calsequestrin 1 (CASQ1) and Ryanodine receptor 1 (RYR1) are two of the main players in excitation-contraction (EC) coupling. CASQ1-knockout mice and mice carrying a mutation in RYR1 (Y522S) linked to human malignant hyperthermia susceptibility (MHS) both suffer lethal hypermetabolic episodes when exposed to halothane (MHS crises) and to environmental heat (heat stroke, HS). The phenotype of Y522S is more severe than that of CASQ1-null mice. As MHS and HS are hypermetabolic responses, we studied the metabolism of adult CASQ1-null and Y522S mice using wild-type (WT) mice as controls. We found that CASQ1-null and Y522S mice have increased food consumption and higher core temperature at rest. By indirect calorimetry, we then verified that CASQ1-null and Y522S mice show an increased oxygen consumption and a lower respiratory quotient (RQ). The accelerated metabolism of CASQ1-null and Y522S mice was also accompanied with a reduction in body fat. Moreover, both mouse models displayed increased oxygen consumption and a higher core temperature during heat stress. The results collected suggest that metabolic rate, oxygen consumption, and body temperature at rest, all more elevated in Y522S than in CASQ1-null mice, could possibly be used as predictors of the level of susceptibility to hyperthermic crises of mice (and possibly humans).

Resistance Training's Ability to Prevent Cancer-induced Muscle Atrophy Extends Anabolic Stimulus.

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 α 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.

Time course of skeletal muscle loss and oxidative stress in rats with Walker 256 solid tumor.

Reactive oxygen species oxidize proteins and modulate the proteasomal system in muscle-wasting cancer cachexia. On day 5 (D5), day 10 (D10), and day 14 (D14) after tumor implantation, skeletal muscle was evaluated. Carbonylated proteins and thiobarbituric acid reactive substances were measured. Chemiluminescence was employed for lipid hydroperoxide estimation. Glutathione, superoxide dismutase, and total radical antioxidant capacity were evaluated. The proteasomal system was assessed by mRNA atrogin-1 expression. Increased muscle wasting, lipid hydroperoxide, and superoxide dismutase, and decreased glutathione levels and total radical antioxidant capacity, were found on D5 in accordance with increased mRNA atrogin-1 expression. All parameters were significantly modified in animals treated with α-tocopherol. The elevation in aldehylde levels and carbonylated proteins observed on D10 were reversed by α-tocopherol treatment. Oxidative stress may trigger signal transduction of the proteasomal system and cause protein oxidation. These pathways may be associated with the mechanism of muscle wasting that occurs in cancer cachexia.

Creatine supplementation does not promote tumor growth or enhance tumor aggressiveness in Walker-256 tumor-bearing rats.

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.

Aerobic exercise training attenuates detrimental effects of cigarette smoke exposure on peripheral muscle through stimulation of the Nrf2 pathway and cytokines: a time-course study in mice.

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.

Resistance Exercise Counteracts Tumor Growth in Two Carcinoma Rodent Models.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.