Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle

0301 basic medicine 0303 health sciences Cell Respiration Mitophagy Antineoplastic Agents DNA, Mitochondrial Article Dexamethasone Mitochondria, Muscle 3. Good health Mice Oxidative Stress 03 medical and health sciences Doxorubicin Mutation Animals Anthracyclines Female Muscle, Skeletal Reactive Oxygen Species Sequence Deletion
DOI: 10.1038/srep08717 Publication Date: 2015-03-03T10:47:15Z
ABSTRACT
Abstract Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but now implicated in causing impaired muscle function long-term survivors. However, no comprehensive assessment of skeletal mitochondrial functions survivors has been performed and the presence persistent chemotherapy-induced dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have used frequently ALL treatment (doxorubicin dexamethasone) up to 4 cycles at 3-week intervals euthanized 3 months after 4th cycle. Treated animals had growth lower mass as well reduced respiration increased reactive oxygen species production per unit consumption. Mitochondrial DNA content protein levels key membrane proteins markers biogenesis unchanged, Parkin reduced. This suggests novel pattern persists because an acquired defect mitophagy signaling. The results could explain observed functional impairments adult may also be relevant other cancers similar regimes.
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