الفهرس 
Title : Effect of Adriamycin on cardiac and skeletal muscles performance. Possible beneficial role of exercise, captopril and dapagliflozin
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Abstract
Background: Doxorubicin (DOX) is an anthracycline antibiotic widely used in treatment of cancer patients.Cardiomyopathyand fatigue are the most popular and serious consequences of DOX therapy. Therefore,in this study the effect of DOX on cardiac and skeletal muscle function was tested. Oxidative stress has been proposed as a working mechanism for DOX-induced toxicity, beside other suggested mechanisms including inflammation, apoptosis and drug induced insulin resistance.Objective: The purpose of this study is to determine the beneficial effect of exercise as a non-pharmacologic approach and sodium glucose cotransporter 2 inhibitors (SGLT2-I) as a newly suggested drug for treatment of heart failure, relative to a well-known drug, angiotensin converting enzyme inhibitors (ACE-I), used in treatment of DOX induced cardiotoxicity. Methods: 56 male rats were divided into 7 groups: group I: control group; group II: DOX was injectedintraperitoneal for 2 weeks in 6 equal injections (each 2.5mg/kg) to induce cardiomyopathy; group III: rats treated with captopril (5 mg/ kg/ day) by gavage for 8 weeks after DOX; group IV: rats were trained for 3 weeks before DOX; group V:ratstrained for 8 weeks after DOX; group VI: rats were trained for 3 weeks before DOXfollowed by 8 weeks after DOX and group VII:rats treated with Dapagliflozin (1.5 mg/ kg/ day) by gavage for 8 weeks after DOX.Parameters of oxidative stress (H2O2, MDA, NO), inflammation (TNF-α, Ang II),antioxidant (catalase), anti-inflammatory (IL-10) and apoptotic factors (caspase 3, p53, NHE-1) were assessed. Also, HOMA-IR was estimated. At the end of this study cardiac and skeletal performance were assessed by EF, CT, 1/2RT and force frequency relationship.Results: The present study showed a deleterious effect of DOX on cardiac and skeletal muscle performance manifested by a significant decrease in EF with significant increase in CT and 1/2RT relative to control; also, H2O2, TNF-α,NO, Ang II, P53, NHE-1, caspase 3 and HOMA-IR were significantly increased with significant decrease in catalase and IL-10. Exercise therapy, ACE-I and SGLT2-I showed significant improvement in all measured parameters relative to DOX.Conclusion: Combined exercise therapy showed the best improvement relative to other groups. ACE-I treatment is still preferred over SGLT2-I in the treatment of heart failure