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

• DOI: 10.1038/srep08717
• Publication Date: 2015-03-03T10:47:15Z
• Authors: Gilles Gouspillou; Celena Scheede-Be...; Sally Spendiff; Madhusudanarao Vuda; Brian Meehan; Heather Mlynarski; Elodie Archer-Lahlou; Nicolas Sgarioto; Fennigje M. Purve...; Yana Konokhova; Janusz Rak; Stéphanie Chevalier; Tanja Taivassalo; Russell T. Hepple; R. Thomas Jagoe
• Keywords: 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

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.