Chemotherapeutic agents induce mitochondrial superoxide production and toxicity but do not alter respiration in skeletal muscle in vitro

Abstract

Chemotherapeutic agents (CAs) can independently promote skeletal muscle dysfunction, fatigue and wasting with mitochondrial toxicity implicated as a possible mechanism. Thus, we aimed to characterise the effects of various CAs on mitochondrial function, viability and oxidant production in C2C12 myoblasts and myotubes. All CAs significantly reduced the viable mitochondrial pool but did not affect mitochondrial functional parameters. Doxorubicin and oxaliplatin increased oxidant production in myotubes while all CAs, except for irinotecan, increased oxidant production in myoblasts and reduced myotube diameter. Our data demonstrate CAs mito-toxic effects, highlighting the potential for mitochondria-protective therapeutics to address chemotherapy-induced skeletal muscle damage.