Effects Of Creatine Supplementation On Doxorubicin-induced Myotoxicity: 101 Board #3 May 31 9

Doxorubicin (DOX) is an effective chemotherapy treatment associated with several deleterious side effects, including skeletal muscle dysfunction. Previous research from our lab has shown that ex vivo creatine (Cr) pretreatment, prior to DOX incubation, attenuated DOX-induced fatigue in the EDL, but not the SOL. The effects of in vivo supplementation on DOX myotoxicity, however, are currently unknown. PURPOSE: To investigate the effects of in vivo Cr supplementation on DOX myotoxicity. METHODS: Male Sprague-Dawley rats were randomly assigned to the control (CON), doxorubicin (DOX), or creatine + doxorubicin (CR+DOX) group. CR+DOX received rodent chow supplemented with 3% creatine monohydrate and the CON and DOX received standard rodent chow. After two weeks of feeding, CR+DOX and DOX groups received a bolus (15 mg/kg) intraperitoneal (i.p.) DOX injection and CON received an i.p. saline injection as a placebo. Dietary interventions then continued for 5 more days. Forelimb grip strength was then measured as an indicator of in vivo muscle function and muscle fatigue was analyzed ex vivo using a 100 second fatigue protocol. RESULTS: When compared to CON, a significantly lower grip strength was observed in DOX (-23%, p<0.05), and creatine monohydrate feeding attenuated this decrement in grip strength (-15% CR+DOX vs. CON, p>0.05). In isolated muscle experiments to explore fatigue, solei (primarily type I muscle) from CON produced significantly less force than baseline at 60 s (p<0.05) and solei from DOX produced significantly less force than baseline at 30 s (p<0.05); however, CR+DOX produced significantly less force than baseline at 60 s (p<0.05) suggesting that Cr feeding attenuated DOX-induced fatigue in type I muscle. In the primarily type II EDL, a significant decline in force production from baseline was observed at 50 s in CON and CR+DOX (p<0.05) and at 20 s in DOX (p<0.05) suggesting that Cr attenuated DOX-induced fatigue in type II muscle. CONCLUSIONS: A diet supplemented with Cr attenuated the decrease in grip strength and increase in fatigue that accompanies DOX treatment. These findings suggest that Cr supplementation may have use in managing DOX myotoxicity in cancer patients.