Exercise and antioxidant supplements in the elderly
Abstract Both exercise and aging increase reactive oxygen species (ROS), which can result in damage to cells. Aging is the result of damage caused by ROS to the mitochondrial genome in post mitotic cells and numerous studies have demonstrated an increase in ROS or their byproducts with exercise. ROS can cause oxidative stress as they overwhelm the antioxidant cellular defenses. Therefore interventions aimed at limiting or inhibiting ROS production, such as supplementation with antioxidant vitamins, should be able to reduce fatigue during muscle contraction and the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. However, it has been …
Inhibition of Xanthine Oxidase by Allopurinol Prevents Skeletal Muscle Atrophy: Role of p38 MAPKinase and E3 Ubiquitin Ligases
International audience; Abstract Top Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS) are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in ratsand its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinaseand the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, …
Allopurinol partially prevents disuse muscle atrophy in mice and humans
AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The pro…
Alopurinol y su papel en el tratamiento de la sarcopenia
Resumen La xantina oxidasa (XO) es la enzima que cataliza la oxidacion de hipoxantina a xantina y de esta a acido urico, por lo que desempena un importante papel en el catabolismo de las purinas. El alopurinol, un analogo de las purinas, es un conocido inhibidor de la XO ampliamente utilizado en la practica clinica para el tratamiento de la gota. Estudios recientes indican que el alopurinol reduce el estres oxidativo y mejora la funcion vascular en diversas enfemedades cardiometabolicas, aumenta el tiempo de ejercicio en pacientes con angina de pecho y mejora la eficiencia de la contractilidad miocardica en la insuficiencia cardiaca. La XO tambien ejerce un papel importante en la generacion…
Rapid hemodilution induced by desmopressin after erythropoietin administration in humans
We have shown that treatment with desmopressin has a very effective hemodilution effect in healthy humans. These results led us to suggest the possible role of desmopressin to mask blood doping in sports. Based on our results, the World Anti-Doping Agency included the desmopressin in the 2011 List of Prohibited Substances and Methods. On this occasion, the aim of our study was to test the desmopressin-induced hemodilution after rHuEpo administration in humans. This was an intra-subject, crossover study in which five physically active males acted as their own controls. A basal blood sample was taken on their first visit to the laboratory. The next day, the subjects began the treatment. They …
Oxidative Stress and Ubiquitin Ligases: their involvement in skeletal muscle atrophy
Introduction Muscle atrophy plays a relevant role in the many very prevalent diseases. Generation of reactive oxygen species (mainly by the xanthine oxidase) and inflammation are two of the main triggers of muscle atrophy. Aim The major aim of our study was to determine the mechanism by which reactive oxygen species activate E3 ubiquitin ligases (MuRF-1 and MAFbx) cause muscle atrophy. Possible prevention by allopurinol, a well-known xanthine oxidase inhibitor widely used in clinical practice; and by indomethacin, a non-steroidal antiinflamatory drug was also studied. Materials and methods Male C57BL/6J mice (3 months old) conditioned by 14 days of hindlimb unloading with or without each tr…
Redox regulation of E3 ubiquitin ligases and their role in skeletal muscle atrophy
Muscle atrophy is linked to reactive oxygen species (ROS) production during hindlimb-unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of our study was to determine the mechanism by which ROS cause muscle atrophy and its possible prevention by allopurinol, a well-known inhibitor of XO widely used in clinical practice, and indomethacin, a nonsteroidal anti-inflammatory drug. We studied the activation of p38 MAP Kinase and NF-?B pathways, and the expression of two E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFb) and Muscle RING Finger-1 (MuRF-1). Male Wistar rats (3 mold) conditioned by 14 days of hindlimb unloading (n=18),…
Redox modulation of mitochondriogenesis in exercise. Does antioxidant supplementation blunt the benefits of exercise training?
Physical exercise increases the cellular production of reactive oxygen species (ROS) in muscle, liver, and other organs. This is unlikely due to increased mitochondrial production but rather to extramitochondrial sources such as NADPH oxidase or xanthine oxidase. We have reported a xanthine oxidase-mediated increase in ROS production in many experimental models from isolated cells to humans. Originally, ROS were considered as detrimental and thus as a likely cause of cell damage associated with exhaustion. In the past decade, evidence showing that ROS act as signals has been gathered and thus the idea that antioxidant supplementation in exercise is always recommendable has proved incorrect.…