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Doxorubicin impairs skeletal muscle mitochondrial respiratory capacity in skeletal muscle
Author(s) -
Gilliam Laura A. A.,
Fisher-Wellman Kelsey H.,
Lin Chien-Te,
Maples Jill M.,
Neufer P. Darrell
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1144.8
Subject(s) - doxorubicin , skeletal muscle , mitochondrion , reactive oxygen species , respiratory chain , mitochondrial ros , respiratory system , endocrinology , pharmacology , medicine , gastrocnemius muscle , biology , chemistry , biochemistry , chemotherapy
Debilitating muscle weakness and fatigue are common side effects of chemotherapy in cancer patients, limiting recovery and increasing morbidity. Our previous work shows that doxorubicin, a common chemotherapy drug, elevates reactive oxygen species (ROS) and decreases contractile force in skeletal muscle. As mitochondria represent a primary source of oxidant generation in muscle, we hypothesized that doxorubicin may compromise mitochondrial respiratory control and increase ROS production. 72 hrs following a single doxorubicin injection (20 mg/kg), maximal ADP‐stimulated O 2 consumption was decreased during respiration supported by palmitoylcarnitine (PC) (−46 ± 26 %, p<0.05) and pyruvate/malate (−43 ± 21 %, p<0.05, n=6/group) in permeabilized fiber bundles (PmFB) from red gastrocnemius muscle. PmFB from doxorubicin treated animals also display increased rates of mitochondrial H 2 O 2 emission with PC (23 ± 2 %) and 3‐phosphoglycerate (49 ± 2 %, p=0.1). Our data indicate that doxorubicin impairs both maximal State 3, and fatty‐acid‐supported respiration. In addition, doxorubicin promotes mitochondrial ROS generation, a potential underlying cause of doxorubicin‐induced muscle dysfunction. Supported by DK073488