Study on Anti-fatigue Effects and Mechanisms of Polysaccharide from Paris polyphylla.

The objectives of this study were to investigate the anti-fatigue effects of Paris polyphylla polysaccharide component 1 (PPPm-1) and explore its mechanisms. A mouse model of exercise-induced fatigue was established by weight-bearing swimming to observe the effects of different concentrations of PPPm-1 on weight-bearing swimming time. The anti-fatigue effect of PPPm-1 was determined by the effects of contraction amplitude, contraction rate, and diastolic rate of the frog gastrocnemius muscle in vivo before and after infiltration with 5 mg/mL PPPm-1. The effects of PPPm-1 on the contents of blood lactate, serum urea nitrogen, hepatic glycogen, muscle glycogen in the exercise fatigue model of mice, and acetylcholine (ACh) content and acetylcholinesterase (AChE) activity at the junction of the frog sciatic nerve-gastrocnemius under normal physiological, and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of the frog gastrocnemius were determined by enzyme-linked immunosorbent assay (ELISA), to investigate the anti-fatigue mechanisms of PPPm-1. The results showed that PPPm-1 could significantly prolong the weight-bearing swimming time in mice (P < 0.01), decrease the contents of blood lactate and serum urea nitrogen, increase the contents of the hepatic glycogen and muscle glycogen of mice after exercise fatigue compared with those of the control group, and there was extremely significant difference in most indicators (P < 0.01). The 5 mg/mL of PPPm-1 could significantly promote the contraction amplitude, contraction rate, and relaxation rate of the gastrocnemius muscle in the frogs, and the content of ACh at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01), but it had obvious inhibitory effetc on the activity of AChE at the junction of the frog sciatic nerve-gastrocnemius (P < 0.01). PPPm-1 could increase the Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of gastrocnemius in the frogs (for Ca2+-Mg2+-ATPase, P < 0.01). The above results suggested that the PPPm-1 had a good anti-fatigue effect, and its main mechanisms were related to improving endurance and glycogen reserve, reducing glycogen consumption, lactate and serum urea nitrogen accumulation, and promoting Ca2+ influx.

Study of anti-fatigue activity of polysaccharide from fruiting bodies of Armillaria gallica.

Fatigue is a common physiological response that is closely related to energy metabolism. Polysaccharides, as excellent dietary supplements, have been proven to have a variety of pharmacological activities. In this study, A 23.007 kDa polysaccharide from Armillaria gallica (AGP) was purified and performed structural characterization, including analysis of homogeneity, molecular weight and monosaccharide composition. Methylation analysis is used to analyze the glycosidic bond composition of AGP. The mouse model of acute fatigue was used to evaluate the anti-fatigue effect of AGP. AGP-treatment improved exercise endurance in mice and reduced fatigue symptoms caused by acute exercise. AGP regulated the levels of adenosine triphosphate, lactic acid, blood urea nitrogen and lactate dehydrogenase, muscle glycogen and liver glycogen of acute fatigue mice. AGP affected the composition of intestinal microbiota, the changes of some intestinal microorganisms are correlated with fatigue and oxidative stress indicators. Meanwhile, AGP reduced oxidative stress levels, increased antioxidant enzyme activity and regulated the AMP-dependent protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathway. AGP exerted an anti-fatigue effect through modulation of oxidative stress, which is related to intestinal microbiota.

Antifatigue effects of Hechong (Tylorrhynchus heterochaetus) through modulation of Nrf2/ARE- mediated antioxidant signaling pathway.

This study was to evaluate the antifatigue effect of T. heterochaetus and explore the underlying mechanism of action. T. heterochaetus extract was treated to mice for 28 days. On the 28th day, after weight loaded swimming test. The levels of antioxidant enzymes and levels of pro- and anti-inflammatory cytokines in the liver and muscles of exercised mice were evaluated. mRNA and protein expression levels of Nrf2, SOD, HO-1, and Keap-1 were evaluated using RT-PCR and western blot analysis. The low (2.70 mg/0.5 ml/20 g) and medium (5.41 mg/0.5 ml/20 g) dose enhanced the activities of antioxidant enzymes like SOD, CAT and GPx in the liver and skeletal muscle thereby enhancing the antifatigue effect. The low and medium doses showed good anti-inflammatory effects by evaluating the levels of pro and anti-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-10 both in the liver and skeletal muscle. Furthermore, RT-PCR and western blot analysis showed increased expression of HO-1, SOD, Nrf2, and decreased expression of Keap-1 gene and proteins in liver and skeletal muscle of T. heterochaetus treated group mice. The current results indicate that T. heterochaetus exert the antifatigue effect through attenuating oxidative stress injury and inflammatory responses through the Nrf2/ARE-mediated signaling pathway.

Mitochondria and Antibiotics: For Good or for Evil?

The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.

A single oral glucose load decreases arterial plasma [K+ ] during exercise and recovery.

AIM: We investigated whether acute carbohydrate ingestion reduced arterial potassium concentration ([K+ ]) during and after intense exercise and delayed fatigue. METHODS: In a randomized, double-blind crossover design, eight males ingested 300 ml water containing 75 g glucose (CHO) or placebo (CON); rested for 60 min, then performed high-intensity intermittent cycling (HIIC) at 130% V˙O2peak , comprising three 45-s exercise bouts (EB), then a fourth EB until fatigue. Radial arterial (a) and antecubital venous (v) blood was sampled at rest, before, during and after HIIC and analyzed for plasma ions and metabolites, with forearm arteriovenous differences (a-v diff) calculated to assess inactive forearm muscle effects. RESULTS: Glucose ingestion elevated [glucose]a and [insulin]a above CON (p = .001), being, respectively, ~2- and ~5-fold higher during CHO at 60 min after ingestion (p = .001). Plasma [K+ ]a rose during and declined following each exercise bout in HIIC (p = .001), falling below baseline at 5 min post-exercise (p = .007). Both [K+ ]a and [K+ ]v were lower during CHO (p = .036, p = .001, respectively, treatment main effect). The [K+ ]a-v diff across the forearm widened during exercise (p = .001), returned to baseline during recovery, and was greater in CHO than CON during EB1, EB2 (p = .001) and EB3 (p = .005). Time to fatigue did not differ between trials. CONCLUSION: Acute oral glucose ingestion, as used in a glucose tolerance test, induced a small, systemic K+ -lowering effect before, during, and after HIIC, that was detectable in both arterial and venous plasma. This likely reflects insulin-mediated, increased Na+ ,K+ -ATPase induced K+ uptake into non-contracting muscles. However, glucose ingestion did not delay fatigue.

The use of a pre-workout supplement containing an amphetamine derivative and its effects on physical performance / Uso de suplemento pre-entrenamiento que contiene un derivado anfetamínico y sus efectos sobre el desempeño físico / Uso de suplemento pré-treino que contém um derivado anfetaminico e seus efeitos sobre o desempenho físico

ABSTRACT Introduction: The quest for better sports performance or simply for esthetic ends has led individuals to seek ergogenic resources indiscriminately to attain their goals. It is believed that nutritional supplements promote better strength, power, focus and better reaction time. Nutritional supplements are used to delay fatigue and increase athletic performance. Also, the anorectics, drugs derived from amphetamines and commonly sought for weight loss, act on the central nervous system by releasing substances that transmit the sensation of not being hungry. Supplements that promise quick solutions to these goals may have compounds in their formulas that compromise health. Objectives: In this study, the potential of creatine and Jack 3D® to boost physical performance and delay muscle fatigue was evaluated in animals that were given the supplements. Methods: The animals underwent 10 weeks of swim training at 80% of the maximum load and received creatine and/or Jack 3D. The muscle contractions were recorded by an electrophysiograph for analysis of muscle fatigue. Results: It was observed that the SED+CR group had significantly different values compared to the SED group and NAT+CR group showed significant differences between groups for the SED, SED+JACK, JACK, NAT and NAT+JACK groups (p <0.05). For the two last parameters, the SED group showed a significant difference in relation to the SED+CR, NAT and NAT+CR groups (p <0.05). Conclusions: These results demonstrate a possible positive influence of physical exercise associated with the use of creatine, delaying muscle fatigue and making an increase in sports performance possible. Level of Evidence III; Development of diagnostic criteria in consecutive patients (with "gold" reference standard applied) .

RESUMEN Introducción: La búsqueda por el mejor desempeño deportivo o simplemente para fines estéticos ha inducido a los individuos a buscar indiscriminadamente recursos ergogénicos para alcanzar el éxito. Se cree que la ingestión de suplementos nutricionales puede proporcionar mayor resistencia, potencia, enfoque y mejor tiempo de reacción. Los suplementos nutricionales son empleados para retardar el surgimiento de la fatiga y aumentar el desempeño atlético. También comúnmente buscados para adelgazamiento están los anorexígenos, medicamentos a base de drogas anfetamínicas, que actúan sobre el sistema nervioso central liberando sustancias que transmiten la sensación de ausencia de hambre. Los suplementos que prometen soluciones rápidas para estos objetivos pueden presentar en sus fórmulas, compuestos que comprometen la salud. Objetivo: En este estudio fue evaluado el potencial de la creatina y del Jack3D® para el desempeño físico y la fatiga muscular de los animales que recibieron la suplementación. Métodos: Los animales fueron sometidos a 10 semanas de entrenamiento de natación a 80% de la carga máxima y recibieron creatina y/o Jack3D. Las contracciones musculares fueron registradas por un electrofisiógrafo para análisis de la fatiga muscular. Resultados: Se observó que el grupo SED+CR presentó valores significativamente diferentes en comparación con el grupo SED y el grupo NAT+CR presentó diferencias significativas con relación a los grupos SED, SED+JACK, NAT y NAT+JACK (p < 0,05). En los dos últimos parámetros, el grupo SED presentó diferencia significativa con relación a los grupos SED+CR, NAT y NAT+CR (p < 0,05). Conclusión: Esos resultados demuestran una posible influencia positiva del ejercicio físico asociado al uso de la creatina, retardando la fatiga muscular y posibilitando un aumento en el desempeño deportivo. Nivel de evidencia III; Desarrollo de criterios diagnósticos en pacientes consecutivos (con estándar de referencia "oro" aplicado) .

RESUMO Introdução: A busca pelo melhor rendimento esportivo ou simplesmente para fins estéticos tem induzido indivíduos a procurarem indiscriminadamente recursos ergogênicos para atingir o êxito. Acredita-se que a ingestão de suplementos nutricionais pode proporcionar maior resistência, potência, foco e melhor tempo de reação. Os suplementos nutricionais são empregados afim de retardar o surgimento da fadiga e aumentar o desempenho atlético. Também comumente procuradas para emagrecimento estão os anorexígenos, medicamentos à base de drogas anfetamínicas, que agem sobre o sistema nervoso central liberando substâncias que transmitem a sensação de ausência de fome. Suplementos que prometem soluções rápidas para estes objetivos podem conter em suas fórmulas compostos que comprometem a saúde. Objetivos: Neste estudo foi avaliado o potencial da creatina e do Jack 3D®para o desempenho físico e fadiga muscular dos animais que receberam a suplementação. Métodos: Os animais foram submetidos a 10 semanas de treinamento de natação a 80% da carga máxima e receberam creatina e/ou Jack 3D. As contrações musculares foram registradas por um eletrofisiógrafo para análise da fadiga muscular. Resultados: Observou-se que o grupo SED+CR apresentou valores significativamente diferentes em comparação com o Grupo SED e o Grupo NAT+CR apresentou diferenças significativas com relação aos grupos SED, SED+JACK, NAT e NAT+JACK (p < 0,05). Nos dois últimos parâmetros, o Grupo SED apresentou diferença significativa com relação aos grupos SED+CR, NAT e NAT+CR (p < 0,05). Conclusão: Esses resultados demonstram uma possível influência positiva do exercício físico associado ao uso da creatina, retardando a fadiga muscular e possibilitando um aumento no desempenho esportivo. Nível de Evidência III; Desenvolvimento de critérios diagnósticos em pacientes consecutivos (com padrão de referência "ouro" aplicado) .

Effect of creatine and sildenafil citrate on the physical performance of mice / Efecto de la creatina y del citrato de sildenafil sobre el desempeño físico de ratones / Efeito da creatina e do citrato de sildenafila sobre o desempenho físico de camundongos

ABSTRACT Introduction: The use of substances to enhance sports performance among professional and amateur athletes is increasing. Such substances may either be included in the group of dietary supplements or fall into pharmacological classes. Every substance used for this purpose is called an ergogenic agent. The number of ergogenic options available increases every day, favoring overuse and use without proper guidance. Among the dietary supplements, we highlight the use of creatine, a substance widespread in sports. Among the pharmacological groups, many drugs are used. Recently the use of sildenafil citrate by professional athletes from various predominantly aerobic sports modalities was reported in the media. Objective: To compare and demonstrate the responses caused by physical training associated with the use of creatine and sildenafil citrate in mice. Methods: A swim training protocol was applied and then an electrophysiograph was used in order to obtain parameters related to contraction intensity, the area under the curve and the percentage drop. Results: The responses obtained demonstrated the ergogenic action of creatine because it altered the parameters used for measurement. The use of sildenafil citrate did not yield satisfactory results to frame the drug as an ergogenic agent. Conclusion: Creatine has an ergogenic effect, reducing the percentage drop after 10 seconds, while sildenafil demonstrated no ergogenic potential and, interestingly, resulted in weaker responses when compared to the exercise groups. Evidence level II; Comparative prospective study .

RESUMEN Introducción: El uso de sustancias con el objetivo de aumentar el rendimiento deportivo entre atletas profesionales y amateurs es creciente. Tales sustancias pueden formar parte del grupo de suplementos alimentarios o integrar clases farmacológicas. Toda sustancia empleada para ese fin es denominada agente ergogénico. El número de opciones entre los agentes ergogénicos aumenta cada día, favoreciendo así su uso excesivo y sin la debida orientación. Entre los suplementos alimentarios, se destaca el uso de creatina, sustancia muy difundida en el medio deportivo. Ya entre los grupos farmacológicos, muchas sustancias son usadas. Recientemente, fue divulgado entre los medios de comunicación el uso de citrato de sildenafil por atletas profesionales, de varias modalidades deportivas, predominantemente las aeróbicas. Objetivos: Comparar y demostrar las respuestas ocasionadas por el entrenamiento físico, asociadas al uso de creatina y citrato de sildenafil en ratones. Métodos: Se aplicó un protocolo de entrenamiento de natación y, a continuación, se usó un electrofisiógrafo con el objetivo de obtener parámetros referentes a la intensidad de contracción, al área bajo la curva y a la caída porcentual. Resultados: Las respuestas obtenidas demuestran acción ergogénica de la creatina, visto que alteraron los parámetros empleados para la medición. Ya el uso de citrato de sildenafil no presentó resultados satisfactorios para encuadrar al fármaco como agente ergogénico. Conclusión: La creatina presenta efecto ergogénico porque reduce la caída porcentual después de 10 segundos, mientras que el sildenafil no presentó potencial ergogénico y, curiosamente, demostró respuestas inferiores cuando comparado a los grupos de ejercicio. Nivel de evidencia II; Estudio prospectivo comparativo .

RESUMO Introdução: O uso de substâncias com o objetivo de aumentar o rendimento esportivo entre atletas profissionais e amadores é crescente. Tais substâncias podem fazer parte do grupo de suplementos alimentares ou integrar classes farmacológicas. Toda substância empregada para esse fim é denominada de agente ergogênico. O número de opções entre os agentes ergogênicos aumenta a cada dia, favorecendo assim o uso em demasia e sem a devida orientação. Entre os suplementos alimentares, salientamos a utilização de creatina, substância muito difundida no meio esportivo. Já entre os grupos farmacológicos, muitas substâncias são utilizadas. Recentemente, foi divulgado entre os meios de comunicação o uso de citrato de sildenafila por atletas profissionais de várias modalidades esportivas, predominantemente as aeróbicas. Objetivos: Comparar e demonstrar as repostas ocasionadas pelo treinamento físico, associadas ao uso de creatina e citrato de sildenafila em camundongos. Métodos: Aplicou-se um protocolo de treinamento de natação e, a seguir, empregou-se um eletrofisiógrafo com objetivo de obter parâmetros referentes à intensidade de contração, à área sob a curva e à queda percentual. Resultados: As respostas obtidas demonstram ação ergogênica da creatina, visto que alteraram os parâmetros empregados para a mensuração. Já a utilização de citrato de sildenafila não apresentou resultados satisfatórios para enquadrar o fármaco como agente ergogênico. Conclusão: A creatina apresenta efeito ergogênico porque reduz a queda percentual após 10 segundos, já a sildenafila não apresentou potencial ergogênico e, curiosamente, demonstrou respostas inferiores quando comparado aos grupos de exercício. Nível de evidência II; Estudo prospectivo comparativo .

The relieving effect of sun-dried protein tonic on sports fatigue / O efeito calmante na fadiga esportiva da proteína tônica secada ao sol / El efecto calmante en la fatiga deportiva de la proteína tónica secada al sol

ABSTRACT Fatigue is a comprehensive process that involves many physiological and biochemical factors. It is a normal physiological reaction when human physical or mental activities reach a certain level. In recent years, it has been verified that free radicals are closely related to exercise-induced fatigue. Cardamine bursa purified selenoprotein has good oxygen-free radical scavenging ability and anti-lipid peroxide. It could protect mitochondria, liver, and red blood cells from peroxide injury. Therefore, it was speculated that the purification of selenoprotein Cardamine may play an active role in attenuating exercise-induced fatigue by scavenging free radicals. This study cleared the selenite protein Capsella bursa (SPC) as a research object, and evaluated its structural characteristics in relieving exercise-induced fatigue. The selenoprotein index system for exercise-induced fatigue was constructed by combining two AHP methods, principal component analysis and factor analysis. Purity, subunit composition, amino acid composition and RCM content were evaluated. The corresponding RCM protein was preliminarily predicted. The results showed that SPCH could significantly prolong the swimming time (P <0.01), improve the lactate clearance capacity (P <0.01), increase the glycogen content of the liver (P <0.01), and reduce the level of the BUN (P <0.05). SPCH has a good effect in relieving exercise-induced fatigue in mice, so it can be considered for development as a nutritional supplement to alleviate exercise-induced fatigue.

RESUMO Fadiga é um processo abrangente envolvendo muitos fatores fisiológicos e bioquímicos. É uma reação fisiológica normal quando as atividades físicas ou mentais humanas atingem um certo nível. Nos últimos anos, verificou-se que os radicais livres estão intimamente relacionados com a fadiga induzida pelo exercício. A selenoproteina purificada de Cardamina bursa tem boa capacidade de depuração de radicais sem oxigénio e de peróxido anti-lípido. Poderia proteger as mitocôndrias, fígado e glóbulos vermelhos de lesões por peróxido. Por conseguinte, especulou-se que a purificação da selenoproteina de Cardamina pode desempenhar um papel activo na atenuação da fadiga induzida pelo exercício por meio de radicais livres de scavenging. Este estudo depurou a proteína selenita Capsella bursa (SPC) como objeto de pesquisa, e avaliou as suas características estruturais no alívio da fadiga induzida pelo exercício. O sistema de índice de selenoproteinas para a fadiga induzida pelo exercício foi construído por meio da combinação dos métodos de AHP, análise principal de componentes e a análise de fatores. Foram avaliados a pureza, a composição sub-unitária, a composição de aminoácidos e o conteúdo do RCM. A proteína correspondente do RCM foi prevista preliminarmente. Os resultados mostraram que o SPCH poderia prolongar significativamente o tempo de natação (P < 0.01), melhorar a capacidade de depuração do lactato (P< 0.01), aumentar o conteúdo do glicogênio do fígado (P < 0.01), e reduzir o nível do BUN (P< 0.05). o SPCH tem um bom efeito em aliviar a fadiga induzida pelo exercício em ratos, de modo que pode ser considerado para desenvolvê-lo como um suplemento nutricional para aliviar a fadiga induzida pelo exercício.

RESUMEN La fatiga es un proceso abarcador que envuelve muchos factores fisiológicos y bioquímicos. Es una reacción fisiológica normal cuando las actividades físicas o mentales humanas alcanzan un cierto nivel. En los últimos anos, se verificó que los radicales libres están íntimamente relacionados con la fatiga inducida por el ejercicio. La selenoproteína purificada de Cardamina bursa tiene buena capacidad de depuración de radicales sin oxígeno y de peróxido antilipídico. Podría proteger las mitocondrias, el hígado y los glóbulos rojos de lesiones por peróxido. Por consiguiente, se especuló que la purificación de la selenoproteína de Cardamina puede desempeñar un papel activo en la atenuación de la fatiga inducida por el ejercicio por medio de radicales libres de scavenging. Este estudio depuró la proteína selenita Capsella bursa (SPC) como objeto de investigación, y evaluó sus características estructurales en el alivio de la fatiga inducida por el ejercicio. El sistema de índice de selenoproteínas para a fatiga inducida por el ejercicio fue construido por medio de la combinación dos métodos de AHP, el análisis principal de componentes y el análisis de factores. Fueron evaluados la pureza, la composición sub-unitaria, la composición de aminoácidos y el contenido del RCM. La proteína correspondiente del RCM fue prevista preliminarmente. Los resultados mostraron que el SPCH podría prolongar significativamente el tiempo de natación (P < 0.01), mejorar la capacidad de depuración del lactato (P< 0.01), aumentar el contenido del glicógeno del hígado (P < 0.01), y reducir el nivel del BUN (P< 0.05). el SPCH tiene un buen efecto en aliviar la fatiga inducida por el ejercicio en ratones, de modo que puede ser considerado para desarrollarlo como un suplemento nutricional para aliviar la fatiga inducida por el ejercicio.

Ganoderic acid alleviates chemotherapy-induced fatigue in mice bearing colon tumor.

Chemotherapy-related fatigue (CRF) is increasingly being recognized as one of the severe symptoms in patients undergoing chemotherapy, which not only largely reduces the quality of life in patients, but also diminishes their physical and social function. At present, there is no effective drug for preventing and treating CRF. Ganoderic acid (GA), isolated from traditional Chinese medicine Ganoderma lucidum, has shown a variety of pharmacological activities such as anti-tumor, anti-inflammation, immunoregulation, etc. In this study, we investigated whether GA possessed anti-fatigue activity against CRF. CT26 tumor-bearing mice were treated with 5-fluorouracil (5-FU, 30 mg/kg) and GA (50 mg/kg) alone or in combination for 18 days. Peripheral and central fatigue-related behaviors, energy metabolism and inflammatory factors were assessed. We demonstrated that co-administration of GA ameliorated 5-FU-induced peripheral muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing glycogen content and ATP production, reducing lactic acid content and LDH activity, and inhibiting p-AMPK, IL-6 and TNF-α expression in skeletal muscle. Co-administration of GA also retarded the 5-FU-induced central fatigue-like behavior accompanied by down-regulating the expression of IL-6, iNOS and COX2 in the hippocampus through inhibiting TLR4/Myd88/NF-κB pathway. These results suggest that GA could attenuate 5-FU-induced peripheral and central fatigue in tumor-bearing mice, which provides evidence for GA as a potential drug for treatment of CRF in clinic.

Effects of heavy-load resistance training during (neo-)adjuvant chemotherapy on muscle cellular outcomes in women with breast cancer.

INTRODUCTION: (Neo-)adjuvant chemotherapy for breast cancer has a deleterious impact on muscle tissue resulting in reduced cardiorespiratory fitness, skeletal muscle mass and function. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training (RT) alone have never been explored. The present study aims to investigate if heavy-load RT during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. We hypothesize that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function, and increase indicators of cellular stress and that RT during treatment will counteract these negative effects. We also hypothesize that RT during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential antitumor myokines and reduce treatment-related side effects on muscle strength and cardiorespiratory fitness. METHODS: Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either randomized to either intervention group or to control group.The intervention group will perform supervised heavy-load RT twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy (T0), after chemotherapy (T1), and 6 months later (T2) for assessment of muscle cellular outcomes. The primary outcome for this study is muscle fiber size. Secondary outcomes are: regulators of muscle fiber size and function, indicators of cellular stress and mitochondrial function, myokines with potential antitumor effects, muscle strength, and cardiorespiratory fitness. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Ethical Review Board in Uppsala, Sweden (Dnr:2016/230/2). Results will be disseminated through presentations at scientific meetings, publications in peer-reviewed journals, social media, and patient organizations. TRIAL REGISTRATION NUMBER: NCT04586517.

A ingestão do anti-inflamatório não esteroide naproxeno afeta parâmetros neuromusculares e metabólicos? / Does the ingestion of naproxen affect neuromuscular and metabolic parameters?

O naproxeno, assim como outros anti-inflamatórios não esteroides (AINEs), está entre os medicamentos mais prescritos no mundo. O objetivo do presente estudo é analisar o efeito da ingestão de naproxeno em parâmetros neuromusculares e determinar seu efeito no dano muscular por meio do uso do marcador lactato. Metodologicamente, foi conduzido um estudo cruzado randomizado, duplo-cego e controlado por placebo em 11 homens treinados em resistência, que realizaram uma sessão de treinamento de força após ingerir 500 mg de naproxeno e outra sessão de treinamento após ingerir um placebo. Os participantes realizaram três séries de supino horizontal com uma carga de 90% da repetição máxima (1RM) até a falha concêntrica. As variáveis de resultado incluíram número de repetições, carga de trabalho e lactato. Os resultados mostraram que há uma correlação positiva e moderada entre as variáveis somatório de repetições e carga total e entre as variáveis lactato e carga total, no grupo naproxeno. No grupo placebo, a correlação positiva e moderada deu-se entre somatório de repetições e carga total. Na análise magnitude baseada nas interferências, as variáveis se mostraram possíveis para uma probabilidade positiva ou trivial e improvável para uma probabilidade negativa. Concluiu-se no presente estudo que o uso do naproxeno como recurso ergogênico no treinamento de força reduz a percepção de fadiga, mas não tem efeito direto no dano muscular, analisado a partir do marcador lactato, logo não interfere de maneira significativa nos parâmetros neuromusculares analisados.

Naproxen, as other non-steroidal anti-inflammatory drugs (NSAIDs), features among the most widely prescribed drugs in the world. The aim of this study is to analyze the effect of naproxen intake on neuromuscular parameters and determine its effect on muscle damage through the use of the lactate marker. In terms of methodology, a randomized, double-blind, placebo-controlled crossover study was conducted on 11 resistance-trained men who underwent a strength training session after taking 500 mg of naproxen and another training session after taking a placebo. The participants performed three sets of horizontal bench presses with a load of 90% maximum repetition (1RM) until concentric failure. Result variables included number of repetitions, workload and lactate. The results showed that there is a positive and moderate correlation between the sum of repetition and total load variables and between lactate and total load variables in the naproxen group. In the placebo group, a positive and moderate correlation was observed between sum of repetitions and total load. In the magnitude analysis, based on the interferences, the variables were shown to be possible for a positive or trivial probability and unlikely for a negative probability. It was concluded that the use of naproxen as an ergogenic resource in strength training reduces the perception of fatigue but has no direct effect on muscle damage when analyzed from the lactate marker, therefore it does not significantly interfere in the analyzed neuromuscular parameters.

Erythromycin has therapeutic efficacy on muscle fatigue acting specifically on orosomucoid to increase muscle bioenergetics and physiological parameters of endurance.

At present, there are still no official or semi-official recommendations for the treatment of muscle fatigue. We previously reported that acute phase protein orosomucoid (ORM) can enhance muscle endurance and exert anti-fatigue effect. In attempting to seek anti-fatigue drugs that target ORM, we found macrolide antibiotics, particularly erythromycin, were effective. Erythromycin can significantly prolong the time of mice forced-swimming and treadmill running, increase muscle fatigue index, alleviate fatigue-induced tissue damage, and elevate glycogen content, mitochondria function and ATP level in the muscle. Also, erythromycin increases ORM protein expression in a dose- and time- dependent manner both in vitro and in vivo. Further studies found that erythromycin could increase the activity of ORM promoter and the stability of ORM mRNA, which might both be responsible for the ORM up-regulation. ORM knockdown or knockout could abolish the promoting effect of erythromycin in mice forced-swimming time, muscle fatigue index and glycogen level. Furthermore, those effects were also abolished in mice with C-C motif chemokine receptor 5 (CCR5) antagonist administration or AMPKα2 deficiency. Therefore, erythromycin could enhance muscle glycogen and endurance via up-regulating the level of ORM and activating CCR5-AMPK pathway, indicating it might act as a potential drug to treat muscle fatigue.

Sea Cucumber Peptides Improved the Mitochondrial Capacity of Mice: A Potential Mechanism to Enhance Gluconeogenesis and Fat Catabolism during Exercise for Improved Antifatigue Property.

Sea cucumber promotes multifaceted health benefits. However, the mechanisms of sea cucumber peptides (Scp) regulating the antifatigue capacity is still unknown. The present study is aimed at further elucidating the effects and mechanisms of Scp on the antifatigue capacity of mice. At first, C57BL/6J mice were assigned into four groups named Con, L-Scp, M-Scp, and H-Scp and received diets containing Scp (0%, 0.15%, 0.3%, and 0.5%, respectively) for continuous 30 days. On the 21th day, a fore grip test was conducted on mice. On the 25th day, a rotating rod test was conducted on mice. On the 30th day, the quantities of glycogen and mitochondrial DNA (mtDNA) were determined in 8 random mice and another 8 mice were forced to swim for 1 hour before slaughter for detecting biochemical indicators. It was observed that the Scp groups significantly prolonged the running time in rotarod, increased forelimb grip strength, improved lactic acid (LD) and urea nitrogen (BUN) levels in the serum, decreased lactic dehydrogenase (LDH) and glutamic oxalacetic transaminase (GOT) activities in the serum, increased blood glucose (BG) and glycogen (GN) levels in the liver and skeletal muscle after swimming, increased the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the skeletal muscle and heart, and improved antioxidant capacity. Furthermore, Scp treatment significantly elevated the mRNA and protein relative levels of power-sensitive factors, lipid catabolism, and mitochondrial biogenesis and significantly upregulated mRNA levels of gluconeogenesis. Besides, mtDNA before the swimming test was increased in the three Scp groups. These results show that Scp treatment has antifatigue capacity. Furthermore, these results suggest that improved energy regulation and antioxidant capacity may be the result of improved mitochondrial function.

Fatigue-induced Fos immunoreactivity within the lumbar cord and amygdala decreases after С60 fullerene pretreatment.

The fundamental aspects related to the mechanisms of action of C60 fullerene nanoparticles on the level of the central nervous system in different experimental conditions are still unclear. Electrophysiological investigation and immunohistochemical techniques of c-fos expression were combined to determine which neural elements within the lumbar segments and in the central nucleus of the amygdala (CeA) are activated under skeletal muscle fatigue development with prior application of C60 fullerenes (dissolved in dimethyl sulfoxide and in distilled water, FDS). After high-frequency electrical stimulation of the triceps surae muscle, the main fatigue-related increases in the c-Fos expression level were registered ipsilaterally within lamina 1 and 5 of the lumbar segments and within the contralateral capsular part of the CeA. C60 fullerene pretreatment in animals with subsequent electrical stimulation induced a distinct (2-4 times) decrease in the level of Fos immunoreactivity in the observed structures in comparison with only fatigue-induced rats. It can be supposed that FDS, as antioxidant compound, can decrease the concentration of free radicals in fatigued tissue and reduce the transmission intensity of nociceptive information from muscles to the spinal cord and amygdala, thereby changing the level of c-Fos expression within the lumbar segments and CeA.

Mangosteen Concentrate Drink Supplementation Promotes Antioxidant Status and Lactate Clearance in Rats after Exercise.

High-strength or long-duration exercise can lead to significant fatigue, oxidative stress, and muscle damage. The purpose of this study was to examine the effect of mangosteen concentrate drink (MCD) supplementation on antioxidant capacity and lactate clearance in rats after running exercise. Forty rats were divided into five groups: N, non-treatment; C, control; or supplemented with MCD, including M1, M5, and M10 (0.9, 4.5, and 9 mL/day) for 6 weeks. The rats were subjected to 30 min running and exhaustive-running tests using a treadmill. The blood lactate; triglyceride; cholesterol and glucose levels; hepatic and muscular malonaldehyde (MDA) levels; and antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), were analyzed. The results of this study demonstrated that MCD supplementation can increase GPx and CAT activities, alleviate oxidative stress in muscle, and increase lactate clearance, and is thereby beneficial to reduced muscle fatigue after exercise.

Yeast Beta-Glucan Supplementation Downregulates Markers of Systemic Inflammation after Heated Treadmill Exercise.

Aerobic exercise and thermal stress instigate robust challenges to the immune system. Various attempts to modify or supplement the diet have been proposed to bolster the immune system responses. The purpose of this study was to identify the impact of yeast beta-glucan (Saccharomyces cerevisiae) supplementation on exercise-induced muscle damage and inflammation. Healthy, active men (29.6 ± 6.7 years, 178.1 ± 7.2 cm, 83.2 ± 11.2 kg, 49.6 ± 5.1 mL/kg/min, n = 16) and women (30.1 ± 8.9 years, 165.6 ± 4.1 cm, 66.7 ± 10.0 kg, 38.7 ± 5.8 mL/kg/min, n = 15) were randomly assigned in a double-blind and cross-over fashion to supplement for 13 days with either 250 mg/day of yeast beta-glucan (YBG) or a maltodextrin placebo (PLA). Participants arrived fasted and completed a bout of treadmill exercise at 55% peak aerobic capacity (VO2Peak) in a hot (37.2 ± 1.8 °C) and humid (45.2 ± 8.8%) environment. Prior to and 0, 2, and 72 h after completing exercise, changes in white blood cell counts, pro- and anti-inflammatory cytokines, markers of muscle damage, markers of muscle function, soreness, and profile of mood states (POMS) were assessed. In response to exercise and heat, both groups experienced significant increases in white blood cell counts, plasma creatine kinase and myoglobin, and soreness along with reductions in peak torque and total work with no between-group differences. Concentrations of serum pro-inflammatory cytokines in YBG were lower than PLA for macrophage inflammatory protein 1ß (MIP-1ß) (p = 0.044) and tended to be lower for interleukin 8 (IL-8) (p = 0.079), monocyte chemoattractment protein 1 (MCP-1) (p = 0.095), and tumor necrosis factor α (TNF-α) (p = 0.085). Paired samples t-tests using delta values between baseline and 72 h post-exercise revealed significant differences between groups for IL-8 (p = 0.044, 95% Confidence Interval (CI): (0.013, 0.938, d = -0.34), MCP-1 (p = 0.038, 95% CI: 0.087, 2.942, d = -0.33), and MIP-1ß (p = 0.010, 95% CI: 0.13, 0.85, d = -0.33). POMS outcomes changed across time with anger scores in PLA exhibiting a sharper decline than YBG (p = 0.04). Vigor scores (p = 0.04) in YBG remained stable while scores in PLA were significantly reduced 72 h after exercise. In conclusion, a 13-day prophylactic period of supplementation with 250 mg of yeast-derived beta-glucans invoked favorable changes in cytokine markers of inflammation after completing a prolonged bout of heated treadmill exercise.

Testosterone improves muscle function of the extensor digitorum longus in rats with sepsis.

Among patients with intensive care unit-acquired weakness (ICUAW), skeletal muscle strength often decreases significantly. The present study aimed to explore the effects of testosterone propotionate on skeletal muscle using rat model of sepsis. Male SD rats were randomly divided into experimental group, model control group, sham operation group and blank control group. Rats in experimental group were given testosterone propionate two times a week, 10 mg/kg for 3 weeks. Maximal contraction force, fatigue index and cross-sectional area of the extensor digitorum longus (EDL) were measured. Myosin, IGF-1, p-AKT and p-mTOR levels in EDL were detected by Western blot. Histological changes of the testis and prostate were detected by hematoxylin and eosin staining. We found that maximal contraction force and fatigue index of EDL in experimental group were significantly higher than in model control group. Cross-sectional area of fast MHC muscle fiber of EDL in group was significantly higher than in model control group. The levels of myosin, IGF-1, p-AKT and p-mTOR of EDL in experimental group were significantly higher than in model control group. In addition, no testicle atrophy and prostate hyperplasia were detected in experimental group. In conclusion, these results suggest that testosterone propionate can significantly improve skeletal muscle strength, endurance and volume of septic rats, and the mechanism may be related to the activation of IGF-1/AKT pathway. Moreover, testosterone propionate with short duration does not cause testicular atrophy and prostate hyperplasia in septic rats. Therefore, testosterone propionate is a potential treatment for muscle malfunction in ICUAW patients.

Artificial oxygen carrier improves fatigue resistance in slow muscle but not in fast muscle in a rat in situ model.

The effects of liposome-encapsulated hemoglobin with high O2 affinity (h-LEH), an artificial O2 carrier in skeletal muscle, were studied by in situ fatigue resistance test in fast-type plantaris (PLT) and slow-type soleus (SOL) muscles with or without ischemia in the rat. The distal tendons of PLT and SOL muscles were isolated in situ and individually attached to the force transducers to record the developed tension in response to stimuli (80 Hz tetanus train, 1.5 minutes) to the ipsilateral sciatic nerve. The fatigue resistance test (five sets separated by 2-minute rests) was evaluated in terms of tension attenuation (fatigue) from the initial to the last tension (A) during each set, attenuation of the initial (B) or last tension (C) in each set, as compared to the first set in the presence or absence of ischemia or h-LEH (10 mL/kg). While ischemia significantly enhanced fatigue only in PLT, h-LEH showed no effect regardless of the perfusion pattern (normal/ischemia) or muscle-type (PLT/SOL) during each set (A). In parameter (B), set-by-set fatigue development was observed in PLT, whereas h-LEH-SOL showed a trend of advanced fatigue resistance. Such trends became clear in the parameter C (last tension), because h-LEH-SOL exerted, rather than decreased, the tension enhancement regardless of the presence or absence of ischemia, whereas there were no h-LEH effects in PLT. In addition, faster recovery of the nicotinamide adenine dinucleotide content in the muscle after 10 minutes of all fatigue tests was observed in h-LEH-SOL, while saline-SOL still showed a significantly higher value than that of control. These results suggested that additional O2 supply by h-LEH may accelerate the tricarboxylic acid cycle/electron transport chain in slow-type aerobic SOL muscle containing abundant mitochondria and contribute to the faster removal of muscle fatigue substances such as lactate.

Effects of Creatine Supplementation on Muscle Fatigue in Rats Receiving Doxorubicin Treatment.

The purpose of this study was to investigate the effects of in vivo creatine monohydrate (Cr) supplementation on doxorubicin (Dox)-induced muscle dysfunction. Male rats were fed a diet supplemented with 3% Cr or a standard chow for 2 wk. After 2 wk of feeding, animals received Dox or saline as a placebo. Five days post-injection, grip strength was measured, and muscle fatigue was analyzed ex vivo. When compared with controls, a significantly lower grip strength was observed with Dox treatment, but no significant handgrip difference was observed with Cr feeding prior to Dox treatment when compared to controls. In the isolated muscle fatigue experiments, solei (primarily type I muscle) from controls produced significantly less force than baseline at 60 s and solei from Dox treated rats produced significantly less force than baseline at 30 s; however, Cr feeding prior to Dox produced significantly less force than baseline at 60 s. In the primarily type II EDL, a decline in force production from baseline was observed at 50 s in controls and Cr + Dox and at 20 s in standard chow + Dox. Cr attenuated the increase in fatigue that accompanies Dox treatment suggesting that Cr supplementation may have use in managing Dox myotoxicity.

Doxorubicin causes lesions in the electron transport system of skeletal muscle mitochondria that are associated with a loss of contractile function.

Doxorubicin is an anthracycline-based chemotherapeutic that causes myotoxicity with symptoms persisting beyond treatment. Patients experience muscle pain, weakness, fatigue, and atrophy, but the underlying mechanisms are poorly understood. Studies investigating doxorubicin-induced myotoxicity have reported disrupted mitochondrial function. Mitochondria are responsible for regulating both cellular energy status and Ca2+ handling, both of which impact contractile function. Moreover, loss of mitochondrial integrity may initiate muscle atrophy. Skeletal muscle mitochondrial dysregulation may therefore contribute to an overall loss of skeletal muscle quality and performance that may be mitigated by appropriately targeted mitochondrial therapies. We therefore assessed the impact of doxorubicin on muscle performance and applied a multiplexed assay platform to diagnose alterations in mitochondrial respiratory control. Mice received a clinically relevant dose of doxorubicin delivered systemically and were euthanized 72 h later. We measured extensor digitorum longus and soleus muscle forces, fatigue, and contractile kinetics in vitro, along with Ca2+ uptake in isolated sarcoplasmic reticulum. Isolated skeletal muscle mitochondria were used for real-time respirometry or frozen for protein content and activity assays. Doxorubicin impaired muscle performance, which was indicated by reduced force production, fatigue resistance, and sarcoplasmic reticulum-Ca2+ uptake, which were associated with a substrate-independent reduction in respiration and membrane potential but no changes in the NAD(P)H/NAD(P)+ redox state. Protein content and dehydrogenase activity results corroborated these findings, indicating that doxorubicin-induced mitochondrial impairments are located upstream of ATP synthase within the electron transport system. Collectively, doxorubicin-induced lesions likely span mitochondrial complexes I-IV, providing potential targets for alleviating doxorubicin myotoxicity.