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Chem Biol Interact. 2016 Mar 5;247:39-48. doi: 10.1016/j.cbi.2016.01.014. Epub 2016 Jan 22.

Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways.

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Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, 35516, Egypt.
Program in Pharmaceutical Sciences, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Mansoura, 35516, Egypt. Electronic address:
Department of Anatomy, Faculty of Medicine, University of Mansoura, 35516, Egypt.
Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, 71491, Saudi Arabia.



The clinical application of the chemotherapeutic agent; Doxorubicin (DOX) is limited by its toxic effects on several body organs. The current study was conducted to evaluate the cardiao-protective effects of crocin, a predominant bioactive constituent of Saffron against DOX-induced myocardial toxicity.


Adult male Sprague Dawley rats received DOX (3.5 mg/kg twice weekly) for 3 weeks with and without daily crocin (10 and 20 mg/kg, orally) for 3 weeks.


DOX injection significantly elevated serum levels of aspartate aminotransferase (AST), cardiac specific-creatine kinase (CK-MB), cardiac Troponin T and lactate dehydrogenase (LDH) with impaired electrocardiogram (ECG) profile, indicating DOX-induced myocardial toxicity. Moreover, cardiac specimen examination revealed myocardial inflammatory infiltration with multifocal areas of myocardial degeneration/necrosis. DOX injection significantly increased numbers of active anti-Cd 68 positivity stained cells and significantly-induced myocardial apoptosis. Finally, there was a significant increase in cardiac TNF-α, IL-1β and caspase-3 expression associated with significant decrease in IL-10. Crocin treatment resulted in a significant dose dependent attenuation of DOX-induced myocardial toxicity. It improved ECG profile and restored normal cardiac architecture. Furthermore, crocin reduced oxidative stress, enhanced host anti-oxidant defenses and decreased apoptosis as well. Additionally, crocin restored the balance between pro-and anti-inflammatory cytokines. The improvement in biochemical parameters was accompanied by significant myocardial improvement as seen in histopathological specimen.


Crocin has a cardioprotective effect against DOX-induced cardiomayopathy. Anti-inflammatory, antioxidant and antiapoptic properties of crocin are thought to be involved in the observed cardioprotective effect.


Caspase-3; Crocin; Doxorubicin; Electrocardiogram; Interleukins; Tumor necrosis factor (TNF)-α

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