Sanchis-Gomar F.,University of Valencia |
Sanchis-Gomar F.,Fundacion Investigacion Hospital Clinico Universitario |
Pareja-Galeano H.,University of Valencia |
Pareja-Galeano H.,Fundacion Investigacion Hospital Clinico Universitario |
And 10 more authors.
Cell Stress and Chaperones | Year: 2015
Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients. © 2014, Cell Stress Society International.
Fiuza-Luces C.,Research Institute Of Hospital 12 Of Octubre I 12 |
Nogales-Gadea G.,Autonomous University of Barcelona |
Garcia-Consuegra I.,Research Institute Of Hospital 12 Of Octubre I 12 |
Pareja-Galeano H.,Research Institute Of Hospital 12 Of Octubre I 12 |
And 10 more authors.
Medicine and Science in Sports and Exercise | Year: 2016
Introduction We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of the McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of "exercise intolerance," is to compare the skeletal muscle tissue of McArdle, heterozygous, and healthy (wild-type [wt]) mice. Methods We analyzed in quadriceps muscle of p.R50X/p.R50X (n = 4), p.R50X/wt (n = 6), and wt/wt mice (n = 5) (all male, 8 wk old) molecular markers of energy-sensing pathways, oxidative phosphorylation and autophagy/proteasome systems, oxidative damage, and sarcoplasmic reticulum Ca 2+ handling. Results We found a significant group effect for total adenosine monophosphate-(AMP)-activated protein kinase (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P = 0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice versus the other two groups. The absence of a massive accumulation of ubiquitinated proteins, autophagosomes, or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice versus the other two groups (P = 0.036), but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P = 0.011). Sarco(endo)plasmic reticulum ATPase 1 levels detected at 110 kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P = 0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated sarco(endo)plasmic reticulum ATPase 1 in p.R50X/p.R50X animals. Conclusion Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca 2+ handling but with no major alterations in oxidative phosphorylation capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions. Copyright © 2016 by the American College of Sports Medicine.