Effects of the Anticancer Drug Doxorubicin and Dietary Creatine Supplementation on Myogenic Regulatory Factor Expression

The purpose of this study was to explore the acute effects of doxorubicin (Dox) treatment on myogenic regulatory factor (MRF) expression and determine the impact that creatine monohydrate (Cr) feeding prior to Dox treatment has on the MRF response. Male Sprague‐Dawley rats were randomly assigned to one of three feeding groups: rodent chow supplemented with 2% Cr for four weeks (Cr1), rodent chow supplemented with 4% Cr for one week followed rodent chow supplemented with 2% Cr for three weeks (Cr2), or standard rodent chow for four weeks (Con). After four weeks, animals in each feeding intervention received a 15 mg/kg bolus Dox i.p. injection or a 0.9% bolus saline i.p. injection as a placebo (Sal). One day after injections, animals were anesthetized, and the extensor digitorum longus (EDL) muscles were excised. Expression of the primary MRFs Myf5 and MyoD and the secondary MRFs myogenin and Mrf4 were then quantified with Western blotting. Creatine feeding promoted an upregulation in Myf5 and MyoD (significant diet effect p=0.022 and p=0.017, respectively), and this upregulation was more profound with MyoD expression in Cr2. Significant diet effects were also observed with myogenin (p=0.0011) and Mrf4 (p<0.001) with Cr1 and Cr2 expressing higher levels of myogenin than Con+Sal (p<0.05) and Cr2 expressing higher levels of Mrf4 than Con+Sal and Con+Dox (p<0.05). In conclusion, Cr feeding prior to Dox treatment increased MRF expression suggesting that Cr may enhance signaling for skeletal muscle repair and regeneration following Dox treatment thereby attenuating muscle damage. Support or Funding Information David 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 .