Glutamine supplementation accelerates functional recovery of EDL muscles after injury by modulating the expression of S100 calcium-binding proteins.

The aim of the current study was to investigate the effect of glutamine supplementation on the expression of HSP70 and the calcium-binding proteins from the S100 superfamily in the recovering extensor digitorum longus (EDL) muscle after injury. Two-month-old Wistar rats were subjected to cryolesion of the EDL muscle and then randomly divided into two groups (with or without glutamine supplementation). Starting immediately after the injury, the supplemented group received daily doses of glutamine (1 g/kg/day, via gavage) for 3 and 10 days orally. Then, muscles were subjected to histological, molecular, and functional analysis. Glutamine supplementation induced an increase in myofiber size of regenerating EDL muscles and prevented the decline in maximum tetanic strength of these muscles evaluated 10 days after injury. An accelerated upregulation of myogenin mRNA levels was detected in glutamine-supplemented injured muscles on day 3 post-cryolesion. The HSP70 expression increased only in the injured group supplemented with glutamine for 3 days. The increase in mRNA levels of NF-κB, the pro-inflammatory cytokines IL-1ß and TNF-α, and the calcium-binding proteins S100A8 and S100A9 on day 3 post-cryolesion in EDL muscles was attenuated by glutamine supplementation. In contrast, the decrease in S100A1 mRNA levels in the 3-day-injured EDL muscles was minimized by glutamine supplementation. Overall, our results suggest that glutamine supplementation accelerates the recovery of myofiber size and contractile function after injury by modulating the expression of myogenin, HSP70, NF-κB, pro-inflammatory cytokines, and S100 calcium-binding proteins.

Glutamine supplementation improves contractile function of regenerating soleus muscles from rats.

This study evaluated the effects of glutamine supplementation immediately after freezing injury on morphological and contractile function of regenerating soleus muscles from rats. Young male Wistar rats were subjected to cryolesion of soleus muscles, and immediately after received a daily supplementation of glutamine (1 g/kg/day). The muscles were evaluated on post-injury days 3 and 10. Glutamine-supplemented injured muscles had a lower number of CD11b positive immune cells and higher mRNA levels of IL-4 compared to those from the cryolesioned muscles analyzed on post-injury day 3. The mRNA and protein expression levels of the myogenic transcription factor MyoD were also higher in glutamine-supplemented injured muscles than in injured muscles examined on post-cryolesion day 3. In addition, glutamine-supplemented injured muscles had a higher size of their regenerating myofibers, attenuated decline in maximum tetanic strength and improved fatigue resistance compared to those from injured muscles evaluated on post-cryolesion day 10. No effect was observed in uninjured muscles supplemented with glutamine. Our results suggest that glutamine supplementation improves the resolution of inflammation, as well as the size and functional recovery of regenerating myofibers from soleus muscles by accelerating the up-regulation of IL-4 and MyoD expression. Future non-pharmacological rehabilitation studies are warranted to investigate the effect of glutamine supplementation on the outcome of injured skeletal muscles.

Acute Effect of Different Duration of Foam Rolling Protocols on Muscle Thickness, Pain Pressure Threshold, and Volume Load on Multiple Sets of Knee Extension.

Previous studies investigated the effects of foam rolling (FR) on measurements of strength and power. However, the acute effect of FR on muscle thickness (MT) and pressure pain threshold (PPT) after multiple sets of resistance exercise remains to be elucidated. The aim of the present study was to examine the effect of one and three minutes of quadriceps FR on muscle thickness (vastus lateralis [VL] and rectus femoris [RF]), pain threshold (VL and RF), and total load lifted (TLL) on multiple sets of knee extension. Nine resistance-trained men (age: 24.8 ± 5.2 years; height: 177 ± 7 cm; total body mass 77.7 ± 6.2 kg) participated the study. MT, PPT, and performance on multiple sets of knee extension were compared after performing passive recovery (CON), one minute (FR1), or three minutes of FR (FR3). A similar total training load among experimental conditions was observed. There was a greater increase on VL muscle thickness after FR3 when compared to CON and FR1. In addition, there was an increase on rectus femoris PPT two minutes post FR3, with no differences between conditions. These results indicate that longer duration FR-protocol may acutely increase muscle thickness of the vastus lateralis muscle without negatively affect the TLL and PTT.

Efeito da suplementação de arginina sobre marcadores indiretos de dano muscular induzido pelo exercício de força / Effect of arginine supplementation on indirect markers of muscle damage induced by resistance exercise

O objetivo do presente estudo foi avaliar o efeito da suplementação de arginina (ARG) sobre marcadores indiretos do dano muscular induzido pelo exercício (DMIE). Participaram do estudo 24 jovens universitários do sexo masculino, com experiência mínima de 1 ano em treinamento de força. Os indivíduos foram alocados em 2 grupos, em seguindo delineamento experimental duplo -cego: suplementado com 7g de arginina (ARG, n=12) ou suplementado com 7g de placebo (PLA, n =12 ). O suplemento foi oferecido 30 min antes da realização do protocolo de 10 séries de 10 repetições máximas (RMs) realizadas no supino. Foram aferidas a circunferência torácica, a dor muscular de in ício tardio (DMIT), por meio da escala visual analógica (EVA), e a carga do teste de uma repetição máxima (1 RM) em repouso, 24h, 48h e 72h após a sessão de treinamento (ST). Os resultados foram analisados utilizando teste de análise de variância ANOVA de dois fatores), seguido pelo teste de Bonferroni. A DMIT apresentou maior magnitude no PLA, em todos momentos avaliados após a ST, em comparação ao grupo ARG (p<0,01). Foi observado maior decréscimo da produção de força no grupo PLA, em 72h após a ST , comparado ao grupo ARG (p<0,05). A suplementação aguda de ARG parece ter atenuado a magnitude da DMIT e acelerado a recuperação da força...(AU)

The purpose of this study was to investigate the effect of arginine (ARG) supplementation o nindirect markers of exercise-induced muscle damage (EIMD). Twenty-four male graduate students, with a minimum of one year of experience in resistance training participated in the study . T he subject s were allocated in 2 groups in a double-blind experimental design: supplemented with 7 g o f argin ine (ARG, n=12) or supplemented with 7g of placebo (PLA, n=12). The dietary supplement was co n sum e d at 3 0 minutes prior to a protocol of 10 sets of 10 maximum repetitions performed in the bench press. Measurements of thoracic circumference, delayed onset muscle soreness (DOMS) using visual an alo gue scale (VAS), and one-repetition maximum (1RM) at rest, 24h, 48h and 72h after the training session (TS). The data were analyzed by ANOVA-two way, followed by the Bonferroni test. DOMS presented a reater magnitude for PLA, in all moments evaluated after TS, compared to the ARG group (p<0.01). There was a greater decrease in the strength for PLA, at 72h after TS, compared to ARG (p<0 .05 ). The acute ARG supplementation seems to attenuate the magnitude of DOMS and accelerate recovery of strength...(AU)

Leucine supplementation improves regeneration of skeletal muscles from old rats.

The decreased regenerative capacity of old skeletal muscles involves disrupted turnover of proteins. This study investigated whether leucine supplementation in old rats could improve muscle regenerative capacity. Young and old male Wistar rats were supplemented with leucine; then, the muscles were cryolesioned and examined after 3 and 10 days. Leucine supplementation attenuated the decrease in the expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4E (eIF4E) in young and old muscles on day 3 post-injury and promoted an increase in the cross-sectional area of regenerating myofibers from both young and old soleus muscles on day 10 post-injury. This supplementation decreased the levels of ubiquitinated proteins and increased the proteasome activity in young regenerating muscles, but the opposite effect was observed in old regenerating muscles. Moreover, leucine decreased the inflammation area and induced an increase in the number of proliferating satellite cells in both young and old muscles. Our results suggest that leucine supplementation improves the regeneration of skeletal muscles from old rats, through the preservation of certain biological responses upon leucine supplementation. Such responses comprise the decrease in the inflammation area, increase in the number of proliferating satellite cells and size of regenerating myofibers, combined with the modulation of components of the phosphoinositide 3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and ubiquitin-proteasome system.

Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle.

This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-ß receptor type I (TßR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TßR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

Leucine supplementation improves skeletal muscle regeneration after cryolesion in rats.

This study was undertaken in order to provide further insight into the role of leucine supplementation in the skeletal muscle regeneration process, focusing on myofiber size and strength recovery. Young (2-month-old) rats were subjected or not to leucine supplementation (1.35 g/kg per day) started 3 days prior to cryolesion. Then, soleus muscles were cryolesioned and continued receiving leucine supplementation until 1, 3 and 10 days later. Soleus muscles from leucine-supplemented animals displayed an increase in myofiber size and a reduction in collagen type III expression on post-cryolesion day 10. Leucine was also effective in reducing FOXO3a activation and ubiquitinated protein accumulation in muscles at post-cryolesion days 3 and 10. In addition, leucine supplementation minimized the cryolesion-induced decrease in tetanic strength and increase in fatigue in regenerating muscles at post-cryolesion day 10. These beneficial effects of leucine were not accompanied by activation of any elements of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin signalling pathway in the regenerating muscles. Our results show that leucine improves myofiber size gain and strength recovery in regenerating soleus muscles through attenuation of protein ubiquitination. In addition, leucine might have therapeutic effects for muscle recovery following injury and in some muscle diseases.

Effect of carbohydrate supplementation on the physiological and perceptual responses to prolonged tennis match play.

Carbohydrate supplementation is a popular nutritional practice used in tennis to enhance physical capacities, motor-skill performance, and delay fatigue. However, the effects of carbohydrate supplementation on physiological and perceptual responses during tennis match play are not established. This double blind, randomized, placebo (PLA)-controlled crossover study was designed to determine the influence of carbohydrate supplementation (0.5 g·kg·h) on glycemia, salivary hormones (cortisol and testosterone) concentration, salivary immunoglobulin A (IgA) concentration, and rating of perceived exertion (RPE) during 3 hours of tennis match play in 12 well-trained tennis players. The only significant difference between the 2 conditions was a lower salivary cortisol concentration postmatch in the carbohydrate trial (p < 0.05); however, there was a trend for higher glucose concentration (p = 0.06) and lower session-RPE (p = 0.08) after tennis match play in the carbohydrate condition, which may have some practical implications. There was no change in salivary testosterone, salivary IgA, and RPE responses during tennis match play between conditions (p > 0.05). These data indicate that carbohydrate ingestion during 3 hours of competitive tennis match play helps to maintain glycemia and attenuates the increase in salivary cortisol concentration compared with PLA.

Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions.

In the present study we have compared the effects of leucine supplementation and its metabolite ß-hydroxy-ß-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB.

GaAs 904-nm laser irradiation improves myofiber mass recovery during regeneration of skeletal muscle previously damaged by crotoxin.

This work investigated the effect of gallium arsenide (GaAs) irradiation (power: 5 mW; intensity: 77.14 mW/cm(2), spot: 0.07 cm(2)) on regenerating skeletal muscles damaged by crotoxin (CTX). Male C57Bl6 mice were divided into six groups (n = 5 each): control, treated only with laser at doses of 1.5 J or 3 J, CTX-injured and, CTX-injured and treated with laser at doses of 1.5 J or 3 J. The injured groups received a CTX injection into the tibialis anterior (TA) muscle. After 3 days, TA muscles were submitted to GaAs irradiation at doses of 1.5 or 3 J (once a day, during 5 days) and were killed on the eighth day. Muscle histological sections were stained with hematoxylin and eosin (H&E) in order to determine the myofiber cross-sectional area (CSA), the previously injured muscle area (PIMA) and the area density of connective tissue. The gene expression of MyoD and myogenin was detected by real-time PCR. GaAs laser at a dose of 3 J, but not 1.5 J, significantly increased the CSA of regenerating myofibers and reduced the PIMA and the area density of intramuscular connective tissue of CTX-injured muscles. MyoD gene expression increased in the injured group treated with GaAs laser at a dose of 1.5 J. The CTX-injured, 3-J GaAs laser-treated, and the CTX-injured and treated with 3-J laser groups showed an increase in myogenin gene expression when compared to the control group. Our results suggest that GaAs laser treatment at a dose of 3 J improves skeletal muscle regeneration by accelerating the recovery of myofiber mass.

Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases.

The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin-proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross-sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS-driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization.