Effects of supplementation with free glutamine and the dipeptide alanyl-glutamine on parameters of muscle damage and inflammation in rats submitted to prolonged exercise

In this study, we investigated the effect of the supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine on plasma levels markers of muscle damage and levels of pro-inflammatory cytokines and glutamine metabolism in rats submitted to prolonged exercise. Rats were submitted to sessions of swim training for 6 weeks. Twenty-one days prior to euthanasia, the animals were supplemented with DIP (n = 8) (1.5 g.kg(-1)), a solution of free L-glutamine (1 g.kg(-1)) and free L-alanine (0.61 g.kg(-1)) (G&A, n = 8) or water (control (CON), n = 8). Animals were killed at rest before (R), after prolonged exercise (PE-2 h of exercise). Plasma concentrations of glutamine, glutamate, tumour necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2) and activity of creatine kinase (CK), lactate dehydrogenase (LDH) and muscle concentrations Of glutamine and glutamate were measured. The concentrations of plasma TNF-alpha, PGE2 and the activity of CK were lower in the G&A-R and DIP-R groups, compared to the CON-R. Glutamine in plasma (p < 0.04) and soleus muscle (p < 0.001) was higher in the DIP-R and G&A-R groups relative to the CON-R group. G&A-PE and DIP-PE groups exhibited lower concentrations of plasma PGE2 (p < 0.05) and TNF-alpha (p < 0.05), and higher concert I rations of glutamine and glutamate in soleus (p < 0.001) and gastrocnemius muscles (p < 0.05) relative to the CON-PE group. We concluded that supplementation with free L-glutamine and the dipeptide LL-alanyl-LL-glutamine represents an effective source of glutamine, which may attenuate inflammation biomarkers after periods of training and plasma levels of CK and the inflammatory response induced by prolonged exercise. Copyright (C) 2009 John Wiley & Sons, Ltd.

Role of spinal microglia in myositis-induced central sensitisation: An immunohistochemical and behavioural study in rats

There is increasing evidence that spinal glial cells play an important role in chronic pain states. However, so far no data on the role of microglia in muscle pain are available. The aim of the present study was to investigate the involvement of spinal microglial cells in chronic muscle pain. In a rat model of chronic muscle inflammation (injection of complete Freunds adjuvant into the gastrocnemius-soleus muscle) alterations of microglia were visualized with quantitative OX-42 immunohistochemistry in the dorsal horn of the segments L4 and L5 12 days after induction of inflammation. In behavioural experiments the influence of chronic intrathecally applied minocycline - a specific microglia inhibitor - or an antibody against tumour necrosis factor-alpha (TNF-alpha: a cytokine released from microglia) on pain-related behaviour was investigated after 1, 3, 6, and 12 days. The immunhistochemical data show that in the deep laminae of the spinal dorsal horn microglial cells reacted with morphological changes to the muscle inflammation. Following inflammation, the mean boundary length surrounding the OX-42 immunostained area was significantly shorter. This indicates that microglial cells were activated by the myositis and withdrew their processes. Chronic intrathecal administration of minocycline or anti TNF-alpha with an osmotic mini-pump largely normalised the inflammation-induced changes in spontaneous exploratory behaviour and attenuated the hypersensitivity to mechanical stimulation. Both the immunohistochemical and behavioural data show that spinal microglial cells are involved in nociceptive processes in the cause of a chronic muscle inflammation. (C) 2008 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Exercise-stimulated GLUT4 Expression is Similar in Normotensive and Hypertensive Rats

The effects of exercise training on systolic blood pressure (BP), insulin sensitivity, and plasma membrane GLUT4 protein content in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. 16 SHR and 16 WKY male rats, aged 6 months, were randomized into sedentary and trained (tread-mill running, 5 days/week, 60 min/day for 10 weeks) groups (n = 8/group). At baseline, SHR had lower insulin sensitivity than WKY rats, however, there were no differences between WKY and SHR GLUT4 expression. The 10-week training reduced BP by similar to 19% in SHR, improved insulin sensitivity by similar to 24% in SHR, but not in WKY, and increased GLUT4 expression in both animal models. Compared to the sedentary group, there was an increase of GLUT4 in WKY rats by similar to 25% in the heart, by similar to 23% in the gastrocnemius, and by similar to 15% in the fat tissue. Trained SHR presented an increase in GLUT4 of similar to 21%, similar to 20%, and similar to 14%, in the same tissues, respectively. There were no differences between SHR and WKY rats in post-training GLUT4 expression. We conclude that training determined BP and insulin resistance reduction in SHR, and increased GLUT4 expression in both normotensive and hypertensive rats. However, considering the similar rise in GLUT4-induced training in SHR and WKY, it is possible that GLUT4 levels in plasma membrane fraction do not have a pivotal role in the exercise-induced improvement of insulin sensitivity in SHR.

Effect of short-term creatine supplementation on markers of skeletal muscle damage after strenuous contractile activity

The protective effect of short-term creatine supplementation (CrS) upon markers of strenuous contractile activity-induced damage in human and rat skeletal muscles was investigated. Eight Ironman triathletes were randomized into the placebo (Pl; n = 4) and creatine-supplemented (CrS; n = 4) groups. Five days prior to the Ironman competition, the CrS group received creatine monohydrate (20 g day(-1)) plus maltodextrin (50 g) divided in two equal doses. The Pl group received maltodextrin (50 g day(-1)) only. The effect of CrS (5 g day(-1)/kg body weight for 5 days) was also evaluated in a protocol of strenuous contractile activity induced by electrical stimulation in rats. Blood samples were collected before and 36 and 60 h after the competition and were used to determine plasma activities of creatine kinase (CK), lactate dehydrogenase (LDH), aldolase (ALD), glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), and C-reactive protein (CRP) level. In rats, plasma activities of CK and LDH, muscle vascular permeability (MVP) using Evans blue dye, muscle force and fatigue were evaluated. Activities of CK, ALD, LDH, GOT, GTP, and levels of CRP were increased in the Pl group after the competition as compared to basal values. CrS decreased plasma activities of CK, LDH, and ALD, and prevented the rise of GOT and GPT plasma activities. In rats, CrS delayed the fatigue, preserved the force, and prevented the rise of LDH and CK plasma activities and MVP in the gastrocnemius muscle. CrS presented a protective effect on muscle injury induced by strenuous contractile activities.

Leucine supplementation favors liver protein status but does not reduce body fat in rats during 1 week of food restriction

An important role in protein-energy metabolism has been attributed to leucine because of its long-term effects on body fat reduction and on the improvement of some indicators of protein status in rodents. The present study investigated the influence of leucine supplementation on the body composition and protein status of rats during the early phase of weight loss, which is characterized by a rapid loss of body weight. Thirty adult male Wistar rats were divided into 2 groups, a control and a leucine group (diet supplemented with 0.59% L-leucine), and were submitted to 1 week of 50% food restriction. The following parameters were evaluated: chemical carcass composition, protein and RNA content in liver and gastrocnemius muscle, and serum concentrations of insulin-like growth factor-1 and corticosterone. A higher liver weight and liver protein content were observed in the supplemented group (p < 0.05). However, no difference in body fat was found between groups (p > 0.05). The results indicate that low-dose leucine supplementation favors liver protein status but does not reduce body fat in rats during the early phase of rapid weight loss.