Effects of Two Creatine Monohydrate Feeding Protocols on Doxorubicin‐Induced Skeletal Muscle Dysfunction

Abstract

The chemotherapy drug doxorubicin (Dox) can negatively impact skeletal muscle function, and interventions to address this side effect are important to improving cancer patient quality of life. The purpose of this study was to investigate the effects of creatine monohydrate (Cr) feeding prior to Dox treatment on skeletal muscle function. Male Sprague‐Dawley rats were randomly assigned to one of four groups: standard chow feeding for four weeks followed by a bolus i.p. 15 mg/kg Dox injection (Dox group); 2% Cr chow feeding for four weeks followed by a bolus i.p. 15 mg/kg Dox injection (Cr1+Dox group); 4% Cr chow feeding for one week then 2% Cr chow feeding for three weeks followed by a bolus i.p. 15 mg/kg Dox injection (Cr2+Dox group); or standard chow feeding for four weeks followed by a bolus i.p. 0.9% NaCl injection to act as a control (Con group). Grip force measurements were obtained prior to the start of nutritional interventions (baseline), prior to injection (after four‐week nutritional intervention), and three days post‐injection. Animals were anesthetized three days post‐injection, the soleus (SOL) and extensor digitorum longus (EDL) muscles were excised, and function was assessed ex vivo using a 100 second fatigue protocol. No grip force differences were observed at baseline or following the four‐week nutritional interventions. Three days after injections, however, the Dox and Cr1+Dox groups had lower grip forces than Con (p<0.05), but this difference was not observed in Cr2+Dox (p>0.05). In the SOL, no between group force differences were observed at baseline or at any of the 10 second time points throughout the fatigue protocol (p>0.05). EDLs from the Dox group generated significantly less force than Con throughout the protocol except the 50 s and 60 s time points (p<0.05). These differences in EDL force production throughout the protocol, however, were not observed in Cr1+Dox and Cr2+Dox (p>0.05). In conclusion, Cr1 and Cr2 feeding protected against Dox‐induced declines in force production in the type II, EDL muscle, and grip force was preserved only with Cr2 feeding. These results suggest that Cr's protection against Dox myotoxicity may be dependent upon Cr dose and skeletal muscle type.Support or Funding InformationDavid S. Hydock, PhD was supported by a Pilot and Exploratory Projects in Palliative Care of Cancer Patients and Their Families, PEP‐17‐193‐01 ‐ PCSM, from the American Cancer Society.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.