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Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms.

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Although it has been previously demonstrated that oxytocin (OXT) receptor stimulation can control skeletal muscle mass in vivo, the intracellular mechanisms that mediate this effect are still poorly understood. Thus, rat oxidative skeletal muscles were isolated and incubated with OXT or WAY-267,464, a non-peptide selective OXT receptor (OXTR) agonist, in the presence or absence of atosiban (ATB), an OXTR antagonist, and overall proteolysis was evaluated. The results indicated that both OXT and WAY-267,464 suppressed muscle proteolysis, and this effect was blocked by the addition of ATB. Furthermore, the WAY-induced anti-catabolic action on protein metabolism did not involve the coupling between OXTR and Gαi since it was insensitive to pertussis toxin (PTX). The decrease in overall proteolysis induced by WAY was probably due to the inhibition of the autophagic/lysosomal system, as estimated by the decrease in LC3 (an autophagic/lysosomal marker), and was accompanied by an increase in the content of Ca2+-dependent protein kinase (PKC)-phosphorylated substrates, pSer473-Akt, and pSer256-FoxO1. Most of these effects were blocked by the inhibition of inositol triphosphate receptors (IP3R), which mediate Ca2+ release from the sarcoplasmic reticulum to the cytoplasm, and triciribine, an Akt inhibitor. Taken together, these findings indicate that the stimulation of OXTR directly induces skeletal muscle protein-sparing effects through a Gαq/IP3R/Ca2+-dependent pathway and crosstalk with Akt/FoxO1 signaling, which consequently decreases the expression of genes related to atrophy, such as LC3, as well as muscle proteolysis.

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Different degrees in the biological activities of Canavalia rosea had been previously reported . In this study, our group assessed the cardioprotective effects of the ethyl acetate fraction (EAcF) of the Canavalia rosea leaves. Firstly, it was confirmed, by in vitro approach, that the EAcF has high antioxidant properties due to the presence of important secondary metabolites, as flavonoids. In order to explore their potential protector against cardiovascular disorders, hearts were previously perfused with EAcF (300 µg.mL-1) and submitted to the global ischemia followed by reperfusion in Langendorff system. The present findings have demonstrated that EAcF restored the left ventricular developed pressure and decreased the arrhythmias severity index. Furthermore, EAcF significantly increased the glutathiones peroxidase activity with decreased malondialdehyde and creatine kinase levels. EAcF was effective upon neither the superoxide dismutase, glutationes reductase nor the catalase activities. In addition, the Western blot analysis revealed that ischemia-reperfusion injury significantly upregulates caspase 3 protein expression, while EAcF abolishes this effect. These results provide evidence that the EAcF reestablishes the cardiac contractility and prevents arrhythmias; it is suggested that EAcF could be used to reduce injury caused by cardiac reperfusion. However more clinical studies should be performed, before applying it in the clinic.

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AIMS: Although it is well established that skeletal muscle contains oxytocin (OT) receptors and OT-knockout mice show premature development of sarcopenia, the role of OT in controlling skeletal muscle mass is still unknown. Therefore, the present work aimed to determine OT's effects on skeletal muscle protein metabolism. MAIN METHODS: Total proteolysis, proteolytic system activities and protein synthesis were assessed in isolated soleus muscle from prepubertal female rats. Through in vivo experiments, rats received 3-day OT treatment (3UI.kg-1.day-1, i.p.) or saline, and muscles were harvested for mass-gain assessment. KEY FINDINGS: In vitro OT receptor stimulation reduced total proteolysis, specifically through attenuation of the lysosomal and proteasomal proteolytic systems, and in parallel activated the Akt/FoxO1 signaling and suppressed atrogenes (e.g., MuRF-1 and atrogin-1) expression induced by motor denervation. On the other hand, the protein synthesis was not altered by in vitro treatment with the OT receptor-selective agonist. Although short-term OT treatment did not change the atrogene mRNA levels, the protein synthesis was stimulated, resulting in soleus mass gain, probably through an indirect effect. SIGNIFICANCE: Taken together, these data show for the first time that OT directly inhibits the proteolytic activities of the lysosomal and proteasomal systems in rat oxidative skeletal muscle by suppressing atrogene expression via stimulation of Akt/FoxO signaling. Moreover, the data obtained from in vivo experiments suggest OT's ability to control rat oxidative skeletal muscle mass.

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ABSTRACT Introduction: High intensity interval training (HIIT) is a method that is widely used today. Objective: The present study aimed to evaluate the effects of HIIT on markers of oxidative stress and muscle damage in rats. Methods: The sample consisted of 60-day-old Wistar rats, divided into two groups: a control group (n=8) and an HIIT group (n=8). The training consisted of fourteen 20-second swimming sessions (loaded with weights equivalent to 14% of their body weight) with 10-second intervals between each session, performed for 12 consecutive days. Results: HIIT induced a reduction (−17.75%) in thiobarbituric acid reactive substances (an oxidative stress marker) in hepatic tissue (p=0.0482). There was also a reduction (−31.80%) in the HIIT group in the level of superoxide dismutase enzyme activity in the liver (p=0.0375). However, there were no differences between the groups in catalase, glutathione peroxidase, glutathione reductase, the total content of SH sulfhydryls, hydroperoxides, or carbonylated proteins in the hepatic tissue. No significant differences were found in any of these markers in the gastrocnemius muscle. The muscle damage markers creatinine kinase and lactate dehydrogenase were also similar between the groups in the gastrocnemius. Conclusion: The conclusion was that that short-term HIIT does not cause oxidative stress or muscle damage. Level of evidence I; High-quality randomized clinical trial with or without statistically significant difference, but with narrow confidence intervals.

RESUMEN Introducción: El entrenamiento en intervalos de alta intensidad (HIIT) es un método muy utilizado actualmente. Objetivo: El presente estudio tuvo como objetivo evaluar los efectos del HIIT en corto plazo sobre marcadores de estrés oxidativo y daño muscular en ratones. Métodos: La muestra consistió en ratones Wistar con 60 días de edad, divididos en dos grupos: grupo control (n = 8) y grupo HIIT (n = 8). El entrenamiento consistió en catorce sesiones de natación de 20 segundos (con cargas equivalentes a 14% del peso corporal) con intervalos de 10 segundos entre cada sesión, realizadas durante 12 días consecutivos. Resultados: El HIIT indujo una reducción (-17,75%) de las sustancias reactivas al ácido tiobarbitúrico (un marcador de estrés oxidativo) en el tejido hepático (p = 0,0482). También hubo reducción (~31,80%) en el grupo HIIT en el nivel de enzima superóxido dismutasa en el hígado (p=0,0375). Sin embargo, no hubo diferencias entre los grupos con relación a catalasa, glutatión peroxidasa, glutatión reductasa, tenor total de sulfhidrilos SH, hidroperóxidos o proteínas carboniladas en el tejido hepático. No fue encontrada ninguna diferencia significativa en ninguno de esos marcadores en el músculo gastrocnemio. Los marcadores de lesión muscular, creatinina quinasa y lactato deshidrogenasa también fueron similares entre los grupos en el gastrocnemio. Conclusión: Fue posible concluir que el HIIT de corta duración no causa estrés oxidativo o daño muscular. Nivel de evidencia I; Estudio clínico aleatorizado de alta calidad con o sin diferencia estadísticamente significativa, pero con intervalos de información estrechos.

RESUMO Introdução: O treinamento intervalado de alta intensidade (HIIT) é um método muito utilizado atualmente. Objetivo: O presente estudo objetivou avaliar os efeitos do HIIT em curto prazo sobre marcadores de estresse oxidativo e dano muscular em ratos. Métodos: A amostra consistiu em ratos Wistar com 60 dias de idade, divididos em dois grupos: grupo controle (n = 8) e grupo HIIT (n = 8). O treinamento consistiu em quatorze sessões de natação de 20 segundos (com cargas equivalentes a 14% do peso corporal) com intervalos de 10 segundos entre cada sessão, realizadas por 12 dias consecutivos. Resultados: O HIIT induziu uma redução (-17,75%) das substâncias reativas ao ácido tiobarbitúrico (um marcador de estresse oxidativo) no tecido hepático (p = 0,0482). Houve também redução (-31,80%) no grupo HIIT no nível de enzima superóxido dismutase no fígado (p = 0,0375). No entanto, não houve diferenças entre os grupos com relação a catalase, glutationa peroxidase, glutationa redutase, teor total de sulfidrilas SH, hidroperóxidos ou proteínas carboniladas no tecido hepático. Nenhuma diferença significativa foi encontrada em qualquer um desses mascadores no músculo gastrocnêmio. Os marcadores de lesão muscular, creatinina quinase e lactato desidrogenase, também foram semelhantes entre os grupos no gastrocnêmio. Conclusão: Foi possível concluir que o HIIT de curta duração não causa estresse oxidativo ou dano muscular. Nível de evidência I; Estudo clínico randomizado de alta qualidade com ou sem diferença estatisticamente significante, mas com intervalos de informação estreitos.

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BACKGROUND: Strength training has beneficial effects on kidney disease, in addition to helping improve antioxidant defenses in healthy animals. OBJECTIVE: To verify if strength training reduces oxidative damage to the heart and contralateral kidney caused by the renovascular hypertension induction surgery, as well as to evaluate alterations in the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) endogenous antioxidant enzymes. METHODS: Eighteen male rats were divided into three groups (n=6/group): sham, hypertensive, and trained hypertensive. The animals were induced to renovascular hypertension through left renal artery ligation. Strength training was initiated four weeks after the induction of renovascular hypertension, continued for a 12-weeks period, and was performed at 70% of 1RM. After the training period, the animals were euthanized and the right kidney and heart were removed for quantitation of hydroperoxides, malondialdehyde and sulfhydryl groups, which are markers of oxidative damage. In addition, the activity of SOD, CAT, and GPx antioxidant enzymes was also measured. The adopted significance level was 5% (p < 0.05). RESULTS: After strength training, a reduction in oxidative damage to lipids and proteins was observed, as could be seen by reducing hydroperoxides and total sulfhydryl levels, respectively. Furthermore, an increased activity of superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzymes was observed. CONCLUSION: Strength training is able to potentially reduce oxidative damage by increasing the activity of antioxidant enzymes. (Arq Bras Cardiol. 2021; 116(1):4-11).

FUNDAMENTO: O treino de força tem efeitos benéficos em doenças renais, além de ajudar a melhorar a defesa antioxidante em animais saudáveis. OBJETIVO: Verificar se o treino de força reduz o dano oxidativo ao coração e rim contralateral para cirurgia de indução de hipertensão renovascular, bem como avaliar as alterações na atividade das enzimas antioxidantes endógenas superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). MÉTODOS: Dezoito ratos machos foram divididos em três grupos (n=6/grupo): placebo, hipertenso e hipertenso treinado. Os animais foram induzidos a hipertensão renovascular através da ligação da artéria renal esquerda. O treino de força foi iniciado quatro semanas após a indução da hipertensão renovascular, teve 12 semanas de duração e foi realizada a 70% de 1RM. Depois do período de treino, os animais foram submetidos a eutanásia e o rim esquerdo e o coração foram retirados para realizar a quantificação de peróxidos de hidrogênio, malondialdeído e grupos sulfidrílicos, que são marcadores de danos oxidativos. Além disso, foram medidas as atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. O nível de significância adotado foi de 5% (p < 0,05). RESULTADOS: Depois do treino de força, houve redução de danos oxidativos a lipídios e proteínas, como pode-se observar pela redução de peróxidos de hidrogênio e níveis sulfidrílicos totais, respectivamente. Além disso, houve um aumento nas atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. CONCLUSÃO: O treino de força tem o potencial de reduzir danos oxidativos, aumentando a atividades de enzimas antioxidantes. (Arq Bras Cardiol. 2021; 116(1):4-11).

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Doxorubicin (DOX) is an anticancer chemotherapy drug that is widely used in clinical practice. It is well documented that DOX impairs baroreflex responsiveness and left ventricular function and enhances sympathetic activity, cardiac sympathetic afferent reflexes and oxidative stress, which contribute to hemodynamic deterioration. Because resistance training (RT)-induced cardioprotection has been observed in other animal models, the objective of this study was to assess the effects of RT during DOX treatment on hemodynamics, arterial baroreflex, cardiac autonomic tone, left ventricular function and oxidative stress in rats with DOX-induced cardiotoxicity. Male Wistar rats were submitted to a RT protocol (3 sets of 10 repetitions, 40% of one-repetition maximum (1RM) of intensity, 3 times per week, for 8 weeks). The rats were separated into 3 groups: sedentary control, DOX sedentary (2.5 mg/kg of DOX intraperitoneal injection, once a week, for 6 weeks) and DOX + RT. After training or time control, the animals were anesthetized and 2 catheters were implanted for hemodynamic, arterial baroreflex and cardiac autonomic tone. Another group of animals was used to evaluate left ventricular function. We found that RT in DOX-treated rats decreased diastolic arterial pressure, heart rate, sympathetic tone and oxidative stress. In addition, RT increased arterial baroreflex sensitivity, vagal tone and left ventricular developed pressure in rats with DOX-induced cardiotoxicity. In summary, RT is a useful non-pharmacological strategy to attenuate DOX-induced cardiotoxicity.

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Resumo Fundamento O treino de força tem efeitos benéficos em doenças renais, além de ajudar a melhorar a defesa antioxidante em animais saudáveis. Objetivo Verificar se o treino de força reduz o dano oxidativo ao coração e rim contralateral para cirurgia de indução de hipertensão renovascular, bem como avaliar as alterações na atividade das enzimas antioxidantes endógenas superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). Métodos Dezoito ratos machos foram divididos em três grupos (n=6/grupo): placebo, hipertenso e hipertenso treinado. Os animais foram induzidos a hipertensão renovascular através da ligação da artéria renal esquerda. O treino de força foi iniciado quatro semanas após a indução da hipertensão renovascular, teve 12 semanas de duração e foi realizada a 70% de 1RM. Depois do período de treino, os animais foram submetidos a eutanásia e o rim esquerdo e o coração foram retirados para realizar a quantificação de peróxidos de hidrogênio, malondialdeído e grupos sulfidrílicos, que são marcadores de danos oxidativos. Além disso, foram medidas as atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. O nível de significância adotado foi de 5% (p < 0,05). Resultados Depois do treino de força, houve redução de danos oxidativos a lipídios e proteínas, como pode-se observar pela redução de peróxidos de hidrogênio e níveis sulfidrílicos totais, respectivamente. Além disso, houve um aumento nas atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. Conclusão O treino de força tem o potencial de reduzir danos oxidativos, aumentando a atividades de enzimas antioxidantes. (Arq Bras Cardiol. 2021; 116(1):4-11)

Abstract Background Strength training has beneficial effects on kidney disease, in addition to helping improve antioxidant defenses in healthy animals. Objective To verify if strength training reduces oxidative damage to the heart and contralateral kidney caused by the renovascular hypertension induction surgery, as well as to evaluate alterations in the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) endogenous antioxidant enzymes. Methods Eighteen male rats were divided into three groups (n=6/group): sham, hypertensive, and trained hypertensive. The animals were induced to renovascular hypertension through left renal artery ligation. Strength training was initiated four weeks after the induction of renovascular hypertension, continued for a 12-weeks period, and was performed at 70% of 1RM. After the training period, the animals were euthanized and the right kidney and heart were removed for quantitation of hydroperoxides, malondialdehyde and sulfhydryl groups, which are markers of oxidative damage. In addition, the activity of SOD, CAT, and GPx antioxidant enzymes was also measured. The adopted significance level was 5% (p < 0.05). Results After strength training, a reduction in oxidative damage to lipids and proteins was observed, as could be seen by reducing hydroperoxides and total sulfhydryl levels, respectively. Furthermore, an increased activity of superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzymes was observed. Conclusion Strength training is able to potentially reduce oxidative damage by increasing the activity of antioxidant enzymes. (Arq Bras Cardiol. 2021; 116(1):4-11)

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Ischemia-reperfusion (I/R) injury causes oxidative stress, leading to severe cardiac dysfunction. Thus, biologically active compounds with antioxidant properties may be viewed as a promising therapeutic strategy against oxidative-related cardiac disorders. Usnic acid (UA), a natural antioxidant, was complexed with ß-cyclodextrin (ßCD) to improve its bioavailability. Wistar male rats were orally treated with the free form of UA (50 mg/kg) or the inclusion complex UA/ßCD (50 mg/kg) for seven consecutive days. Afterward, hearts were subjected to I/R injury, and the cardiac contractility, rhythmicity, infarct size, and antioxidant enzyme activities were evaluated. Here, we show that neither UA nor UA/ßCD treatments developed signs of toxicity. After I/R injury, animals treated with UA/ßCD showed improved post-ischemic cardiac functional recovery while the release of cell injury biomarkers decreased. Following reduced cardiac damage, a lower incidence of ventricular arrhythmias and smaller myocardial infarct size were associated with reduced lipid peroxidation, along with preserved activity of antioxidant enzymes compared to untreated rats. Surprisingly, uncomplexed UA did not protect hearts against IR injury. Altogether, our results indicate that the inclusion complex UA/ßCD is a critical determining factor responsible for the cardioprotection action of UA, suggesting the involvement of an antioxidant-dependent mechanisms. Moreover, our findings support that UA/ßCD is a structurally engineered compound with active cardioprotective properties.

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The aim of this study is to investigate the effects of limonene, alone or associated with therapeutic ultrasound, on oxidative stress following skeletal muscle injury. Thirty male Wistar rats were divided into 5 groups: CTR-control, MI-muscle injury without treatment, TPU-therapeutic pulsed ultrasound alone, TPU + LIM-phonophoresis with 5% limonene, and LIM-5% limonene applied topically. Muscle injury was induced by a mechanical abrupt impact over gastrocnemius muscle. The animals were treated in the following intervals: 2, 12, 24, 48, 72, and 96 h after injury. Blood and gastrocnemius samples were collected 98 h after lesion for data analysis. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity, lipid peroxidation (TBARS) levels, catalase (CAT), and superoxide dismutase (SOD) activity were assessed. CK (p = 0.01), SOD activity (p < 0.01), and TBARS levels (p < 0.01) were increased after injury. There was no effect on LDH levels in any group. Phonophoresis (TABRS p < 0.01; SOD p = 0.01), TPU alone (TBARS p < 0.01; SOD p = 0.01), and LIM alone (TBARS p < 0.01; SOD p < 0.01) reduced TBARS levels and SOD activity after muscle injury. There was no change for CAT activity after injury. Only phonophoresis reduced CK activity after injury (p < 0.01). There was no difference between phonophoresis, TPU alone and LIM alone groups for TBARS, SOD, CAT, and LDH. Limonene alone and TPU alone were effective in reducing oxidative stress parameters after skeletal muscle injury. Only phonophoresis decreased CK activity. Skeletal muscle injury increases reactive oxidative species (ROS) levels and muscle proteins activity as creatine kinase (CK) and lactate dehydrogenase (LDH). Five percent limonene, alone or associated with therapeutic pulsed ultrasound, exhibited reduction of CK, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation markers (TBARS). Graphical abstract.

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