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

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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