الفهرس 
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Abstract
Background and aims: Cardiomyopathies are a broad range of myocardial disorders characterized by structural or functional abnormalities. One of the most potent medications used to treat both adult and pediatric malignancies is doxorubicin (DOX) that head to cardiotoxicity. The aim of this study was to clarify the role of fasting and NC in doxorubicin-induced cardiomyopathy. Methods: 48 adult male rats were divided into six groups; i) control group, ii) ADF group, iii) NC Group, iv) Dox group, v) DOX+ADF groupAnd vi): ΙV: DOX+NC Group: rats were injected with 0.2 mg/kg NC I.P daily, 2hrs prior to Dox injection. By the end of the experiment, rats were subjected to ECG and Echo recording, blood samples were collected for cardiac enzymes (CK-MB, LDH), and tissue samples for oxidative stress (MDA, catalase, and GSH reductase), histopathological examination and immunohistochemistry for (LC3, caspase3, and beclin1), electron microscopic examination. Also, the metabolic markers AMPK via Elisa and acetyl Co-A carboxylase via PCR were measured.Results: DOX group showed a significant rise in both cardiac enzymes (CK-MB and LDH), myocardial MDA, anti-acetyl Co-A carboxylase, and histopathological damage and increased immune staining of caspase-, beclin-1 and LC3) besides a significant decline in antioxidants (catalase) and AMPK in comparison with the control group. ECG traces of rats in the DOX-induced cardiomyopathy showed prolonged corrected QT interval and decreased heart rate. Echo recording showed decreased ejection fraction and fractional shortening in the DOX group. Application of fasting and NC on the DOX model caused more favorable substantial advances in the measured parameters.Conclusions: Either ADF or NC may preserve the cardiac functions and structure in DOX-induced cardiomyopathy. This effect could be due to suppression of myocardial oxidative stress and apoptosis as well as autophagy regulation (via downregulation of Beclin-1 and LC3). Activation of AMPK might play an important role in autophagy regulation in cardiac muscle. However, ADF and NC have similar significant effects, but ADF had more metabolic role and NC had more antioxidant role.