Aerobic exercise, but not metformin, prevents reduction of muscular performance by AMPk activation in mice on doxorubicin chemotherapy

Autor(es)

de Lima, Jr., Edson A. ^[1] ; de Sousa, Luis G. O. ^[2] ; Teixeira, Alexandre Abilio de S. ^[1] ; Marshall, Andrea G. ^[2] ; Zanchi, Nelo E. ^[3] ; Rosa Neto, Jose C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Cell & Dev Biol, Immunometab Res Grp, Ave Prof Lineu Prestes 1524, BR-05508900 Sao Paulo - Brazil

^[2] Univ Iowa, Dept Internal Med, Div Endocrinol & Metab, Iowa City, IA 52242 - USA

^[3] Fed Univ Maranhao UFMA, Dept Phys Educ, Lab Cellular & Mol Biol Skeletal Muscle LABCEMME, Sao Luis, Maranhao - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 233, n. 12, p. 9652-9662, DEC 2018.
• Citações Web of Science: 2

Resumo

Doxorubicin (DOX) is a chemotherapy agent widely used in clinical practice, and it is very efficient in tumor suppression, but the use of DOX is limited by a strong association with the development of severe muscle atrophy and cardiotoxicity effects. Reversion or neutralization of the muscular atrophy can lead to a better prognosis. Recent studies have proposed that the negative effect of DOX on skeletal muscle is linked to its inhibition of AMP-activated protein kinase (AMPk), a key mediator of cellular metabolism. On the basis of this, our goal was to evaluate if aerobic exercise or metformin treatment, activators of AMPk, would be able to attenuate the deleterious effects on skeletal muscle induced by the DOX treatment. C57BL6 mice received either saline (control) or DOX (2.5mg/kg body weight) intraperitoneally, twice a week. The animals on DOX were further divided into groups that received adjuvant treatment in the form of moderate aerobic physical exercise (DOX+T) or metformin gavage (300mg/body weight/day). Body weight, metabolism, distance run, muscle fiber cross-sectional area (CSA), and protein synthesis and degradation were assessed. We demonstrated that aerobic training, but not metformin, associated with DOX increased the maximal aerobic capacity without changing muscle mass or fiber CSA, rescuing the muscle fatigue observed with DOX treatment alone. This improvement was associated with AMPk activation, thus surpassing the negative effects of DOX on muscle performance and bioenergetics. In conclusion, aerobic exercise increases AMPk activation and improved the skeletal muscle function, reducing the side effects of DOX. (AU)

• Processo FAPESP: 13/09367-4 - Efeitos metabólicos da doxorrubicina no músculo esquelético e tecido adiposo: possível papel adjuvante do treinamento físico e metformina
• Beneficiário: José Cesar Rosa Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/17068-2 - Efeito do treinamento físico aeróbio associado ao tratamento quimioterápico com doxorrubicina em camundongos com carcinoma de pulmão Lewis (LLC). Papel da adiponectina no músculo estriado esquelético e no tumor.
• Beneficiário: Edson Alves de Lima Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado