RESUMO
BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.
Assuntos
Acetilcisteína , Hipertensão , NADPH Oxidases , Estresse Oxidativo , Ratos Endogâmicos SHR , Remodelação Ventricular , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Acetilcisteína/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Hipertensão/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Ratos , Antioxidantes/farmacologia , Condicionamento Físico Animal , Modelos Animais de Doenças , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Miocárdio/metabolismo , Miocárdio/patologia , Peróxidos Lipídicos/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Suplementos Nutricionais , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Hipertrofia Ventricular Esquerda/metabolismoRESUMO
A T-cell-independent (TI) pathway activated by microbiota results in the generation of low-affinity homeostatic IgA with a critical role in intestinal homeostasis. Moderate aerobic exercise (MAE) provides a beneficial impact on intestinal immunity, but the action of MAE on TI-IgA generation under senescence conditions is unknown. This study aimed to determine the effects of long-term MAE on TI-IgA production in young (3 month old) BALB/c mice exercised until adulthood (6 months) or aging (24 months). Lamina propria (LP) from the small intestine was obtained to determine B cell and plasma cell sub-populations by flow cytometry and molecular factors related to class switch recombination [Thymic Stromal Lymphopoietin (TSLP), A Proliferation-Inducing Ligand (APRIL), B Cell Activating Factor (BAFF), inducible nitric oxide synthase (iNOS), and retinal dehydrogenase (RDH)] and the synthesis of IgA [α-chain, interleukin (IL)-6, IL-21, and Growth Factor-ß (TGF-ß)]; and epithelial cells evaluated IgA transitosis [polymeric immunoglobulin receptor (pIgR), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-4] by the RT-qPCR technique. The results were compared with data obtained from sedentary age-matched mice. Statistical analysis was computed with ANOVA, and p < 0.05 was considered to be a statistically significant difference. Under senescence conditions, MAE promoted the B cell and IgA+ B cells and APRIL, which may improve the intestinal response and ameliorate the inflammatory environment associated presumably with the downmodulation of pro-inflammatory mediators involved in the upmodulation of pIgR expression. Data suggested that MAE improved IgA and downmodulate the cytokine pro-inflammatory expression favoring homeostatic conditions in aging.
Assuntos
Envelhecimento , Homeostase , Imunoglobulina A , Camundongos Endogâmicos BALB C , Condicionamento Físico Animal , Animais , Imunoglobulina A/metabolismo , Imunoglobulina A/imunologia , Camundongos , Envelhecimento/imunologia , Citocinas/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Fator Ativador de Células B/metabolismo , Fator Ativador de Células B/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Masculino , Plasmócitos/imunologia , Plasmócitos/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genéticaRESUMO
This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling.
Assuntos
Fator de Indução de Apoptose , Apoptose , Jejum , Treinamento Intervalado de Alta Intensidade , Fibras Musculares de Contração Lenta , Atrofia Muscular , Miostatina , Ratos Wistar , Transdução de Sinais , Animais , Masculino , Apoptose/fisiologia , Jejum/metabolismo , Jejum/fisiologia , Miostatina/metabolismo , Treinamento Intervalado de Alta Intensidade/métodos , Ratos , Transdução de Sinais/fisiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Fator de Indução de Apoptose/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Rápida/patologia , Endodesoxirribonucleases/metabolismo , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Músculo Esquelético/metabolismo , Jejum Intermitente , Poli(ADP-Ribose) Polimerase-1RESUMO
BACKGROUND: Exercise-induced pulmonary haemorrhage (EIPH) in athletic horses is characterized by the presence of blood from the lungs in the tracheobronchial tree after intense exercise. Despite the high prevalence of EIPH in horses, the primary aetiology remains unknown. Variants in the genes encoding CD39 and CD39L1 (ENTPD1 and ENTPD2, respectively) were previously reported as potential genetic causes involved in EIPH pathogenesis. However, the role of these variants in haemostatic functions is unknown. RESULTS: To investigate the association between EIPH and missense variants in the ENTPD1 (rs1152296272, rs68621348, and rs68621347) and ENTPD2 genes (rs782872967), 76 Thoroughbred horses diagnosed with EIPH and 56 without clinical signs of EIPH (control group) by trachea-bronchial endoscopy were genotyped. The rs1152296272 and rs68621347 variants were linked, which explained why the same results were found in all horses. Approximately 96% and 95% of the EIPH and control horses, respectively, carried at least one nonreference allele for these variants. In contrast, 100% of the control horses and 96% of the EIPH horses were homozygous for the reference allele for the rs68621348 variant. In the EIPH group, 1.5% of the horses were homozygotes and 24% were heterozygous for the nonreference allele of the rs782872967 variant. In the control group, the nonreference allele of this variant was observed only in heterozygotes (16%). There were no significant differences between groups for any of the variants. CONCLUSIONS: The variants previously described in the genes encoding the CD39 and CD39L1 enzymes were highly present in the studied population. However, no association was found between the occurrence of EIPH and the presence of these variants in Thoroughbred horses in this study.
Assuntos
Hemorragia , Doenças dos Cavalos , Pneumopatias , Condicionamento Físico Animal , Animais , Cavalos , Doenças dos Cavalos/genética , Hemorragia/veterinária , Hemorragia/genética , Pneumopatias/veterinária , Pneumopatias/genética , Masculino , Apirase/genética , Feminino , Predisposição Genética para Doença , Genótipo , Mutação de Sentido IncorretoRESUMO
This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (VÌO2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher VÌO2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved VÌO2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.
Assuntos
Dislipidemias , Consumo de Oxigênio , Condicionamento Físico Animal , Triglicerídeos , Animais , Masculino , Camundongos , Dislipidemias/metabolismo , Dislipidemias/terapia , Dislipidemias/genética , Hipertrigliceridemia/terapia , Hipertrigliceridemia/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Consumo de Oxigênio/fisiologia , Condicionamento Físico Animal/fisiologia , Triglicerídeos/sangueRESUMO
Atmospheric pollution can be defined as a set of changes that occur in the composition of the air, making it unsuitable and/or harmful and thereby generating adverse effects on human health. The regular practice of physical exercise (PE) is associated with the preservation and/or improvement of health; however, it can be influenced by neuroimmunoendocrine mechanisms and external factors such as air pollution, highlighting the need for studies involving the practice of PE in polluted environments. Herein, 24 male C57BL/6 mice were evaluated, distributed into four groups (exposed to a high concentration of pollutants/sedentary, exposed to a high concentration of pollutants/exercised, exposed to ambient air/sedentary, and exposed to ambient air/exercised). The exposure to pollutants occurred in the environmental particle concentrator (CPA) and the physical training was performed on a treadmill specially designed for use within the CPA. Pro- and anti-inflammatory markers in blood and bronchoalveolar lavage (BALF), BALF cellularity, and lung tissue were evaluated. Although the active group exposed to a high concentration of pollution showed a greater inflammatory response, both the correlation analysis and the ratio between pro- and anti-inflammatory cytokines demonstrated that the exercised group presented greater anti-inflammatory activity, suggesting a protective/adaptative effect of exercise when carried out in a polluted environment.
Assuntos
Poluentes Atmosféricos , Líquido da Lavagem Broncoalveolar , Citocinas , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal , Animais , Masculino , Camundongos , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Inflamação/induzido quimicamente , Pulmão/efeitos dos fármacos , Poluição do Ar/análise , Poluição do Ar/efeitos adversos , Material Particulado/toxicidade , Material Particulado/análiseRESUMO
The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Mitocôndrias , Estresse Oxidativo , Condicionamento Físico Animal , Ratos Wistar , Animais , Feminino , Ratos , Mitocôndrias/metabolismo , Gravidez , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estresse do Retículo Endoplasmático , Biomarcadores/metabolismo , Córtex Pré-Frontal/metabolismo , Músculo Esquelético/metabolismo , Desnutrição/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fator 6 Ativador da Transcrição/metabolismoRESUMO
The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.
Assuntos
Farinha , Interleucina-6 , Músculo Esquelético , Miocinas , Treinamento Resistido , Animais , Humanos , Masculino , Camundongos , Composição Corporal/efeitos dos fármacos , Metabolismo Energético , Fibronectinas/metabolismo , Fibronectinas/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Miocinas/genética , Miocinas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Condicionamento Físico Animal , Termogênese/efeitos dos fármacosRESUMO
Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2α/eIF2α). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2α/eIF2α protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle.NEW & NOTEWORTHY Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10's role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.
Assuntos
Envelhecimento , Estresse do Retículo Endoplasmático , Interleucina-10 , Músculo Esquelético , Condicionamento Físico Animal , Animais , Masculino , Camundongos , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Inflamação/metabolismo , Interleucina-10/metabolismo , Interleucina-10/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Músculo Quadríceps/metabolismo , Resposta a Proteínas não Dobradas/fisiologiaRESUMO
Molecular mechanisms associated to improvement of metabolic syndrome (MetS) during exercise are not fully elucidated. MetS was induced in 250 g male Wistar rats by 30% sucrose in drinking water. Control rats receiving tap water were controls, both groups received solid standard diet. After 14 weeks, an endurance exercised group, and a sedentary were formed for 8 weeks. The soleus and extensor digitorum longus (EDL) muscles were dissected to determine contractile performance, expression of myosin heavy chain isoforms, PGC1α, AMPKα2, NFATC1, MEF2a, SIX1, EYA1, FOXO1, key metabolic enzymes activities. Exercise mildly improved MetS features. MetS didn't alter the contractile performance of the muscles. Exercise didn't altered expression of PGC1α, NFATC1, SIX1 and EYA1 on MetS EDL whereas NFATC1 increased in soleus. Only citrate synthase was affected by MetS on the EDL and this was partially reverted by exercise. Soleus α-ketoglutarate dehydrogenase activity was increased by exercise but MetS rendered the muscle resistant to this effect. MetS affects mostly the EDL muscle, and endurance exercise only partially reverts this. Soleus muscle seems more resilient to MetS. We highlight the importance of studying both muscles during MetS, and their metabolic remodeling on the development and treatment of MetS by exercise.