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Hydock, David

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Doxorubicin (DOX) is a powerful chemotherapy agent that is associated with a number of deleterious side effects, including skeletal muscle dysfunction. The exact mechanisms behind the observed skeletal muscle dysfunction have yet to be fully understood. Nonetheless, the observed myotoxicity is believed to be the result of an increased oxidative stress. Resistance training (RT) has been shown to preserve skeletal muscle function in DOX treated muscles. Conversely, creatine (Cr) has been shown to improve skeletal muscle function. Yet, there has been no investigation into the effect of combined RT and Cr on DOX-induced muscle dysfunction. Thus, the possibility exists that in combination, Cr and RT could attenuate the myotoxic effects of DOX beyond that of when the interventions are administered separately. PURPOSE: To investigate the effects of prior RT and Cr treatment on DOX-induced skeletal muscle dysfunction. METHODS: Male Sprague-Dawley rats were randomly assigned to a RT or sedentary group. Resistance training was simulated by using an elevated food model. After six weeks of training, the soleus (SOL) and extensor digitorum longus (EDL) were excised and placed in an ex vivo tissue bath containing a Krebs buffer (K) where initial force was measured. Muscles were then incubated with either K or a K containing Cr (25 mM) for 30 minutes. The buffers were refreshed with either new K or K containing DOX (24 μM) and incubated for 30 minutes. Muscles were then supplied with new K and twitch force data were collected. The muscles were again supplied with fresh K and subjected to a 100 sec fatigue protocol where force production was recorded every 10 seconds to analyze fatigue. After functional data were collected, tissues were analyzed for total Cr content. RESULTS: This study failed to demonstrate DOX-induced muscle dysfunction on maximal twitch characteristics but DOX-induced dysfunction did become apparent under prolonged stimulation. Furthermore, this investigation demonstrated that, in combination, RT and Cr could significantly attenuate fatigue in the DOX treated muscle. This study also failed to show any significant change total intracellular Cr after incubation with Cr or prior RT. CONCLUSION: Evidence from this study provides insight into the effectiveness of a combined treatment with RT and Cr to minimize fatigue and offset the myotoxic effects of DOX. Such evidence provides more support to the effectiveness and capacity of exercise interventions to improve functioning of cancer patients during their treatment process.




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