Direct effects of doxorubicin on skeletal muscle contribute to fatigue.
Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation followed in time by contraction impediment, which could be explained by DOX-induced changes in Ca(2+) responses of myotubes in vitro. The Ca(2+) responses in skeletal muscle, however, could not be explained by oxidative stress.
van Norren
K
K
Danone Research, Centre for Specialised Nutrition (formerly known as Numico Research), Wageningen, The Netherlands. Klaske.vanNorren@Danone.com
van Helvoort
A
A
Argilés
J M
JM
van Tuijl
S
S
Arts
Karin
K
Gorselink
M
M
Laviano
A
A
Kegler
D
D
Haagsman
H P
HP
van der Beek
E M
EM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D005221:Fatigue / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010805:Physical Conditioning, Animal
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D002118:Calcium