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Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

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Cell Stress and Chaperones Aims and scope

Abstract

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.

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Abbreviations

ADM:

Adrenomedullin

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

ATP:

Adenosine triphosphate

CK:

Creatine kinase

CK-MB:

Creatine kinase, myocardic isoenzyme

CoP:

Copeptin

CRP:

C-reactive protein

FRs:

Free radicals

GDF15:

Growth differentiation factor 15

GGT:

Gamma glutamyltransferase

HSP:

Heat-shock protein

HO:

Heme oxygenase

Hs-TnT:

Highly sensitive troponin T

IL-6:

Interleukin-6

IMP:

Inositol monophosphate

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

MR-proADM:

Midregional part of proadrenomedullin

Myo:

Myoglobin

NAD:

Nicotinamide adenine dinucleotide

OS:

Oxidative stress

PCT:

Procalcitonin

PlGF:

Placental growth factor

ROS:

Reactive oxygen species

suPAR:

Soluble urokinase plasminogen activator receptor

sVEGFR-1/sFLT-1:

Vascular endothelial growth factor receptor-1

VEGF:

Vascular endothelial growth factor

XDH:

Xanthine dehydrogenase

XO:

Xanthine oxidase

XOR:

Xanthine oxide-reductase

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Authors and Affiliations

  1. Department of Physiology, University of Valencia, Av. Blasco Ibañez, 15, Valencia, 46010, Spain

    F. Sanchis-Gomar & H. Pareja-Galeano

  2. Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain

    F. Sanchis-Gomar & H. Pareja-Galeano

  3. University Research Institute “Dr. Viña Giner”, Molecular and Mitochondrial Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain

    C. Perez-Quilis

  4. Department of Biomedical Sciences, University of León, León, Spain

    A. Santos-Lozano

  5. Research Institute of Hospital 12 de Octubre (“i + 12”), Madrid, Spain

    A. Santos-Lozano, C. Fiuza-Luces, N. Garatachea & A. Lucia

  6. European University, Madrid, Spain

    C. Fiuza-Luces & A. Lucia

  7. University of Zaragoza, Huesca, Spain

    N. Garatachea

  8. Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy

    G. Lippi

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  1. F. Sanchis-Gomar
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Sanchis-Gomar, F., Pareja-Galeano, H., Perez-Quilis, C. et al. Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?. Cell Stress and Chaperones 20, 3–13 (2015). https://doi.org/10.1007/s12192-014-0543-2

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