title: Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, 35516, Egypt.
authors.forename: Nehal M
authors.initials: NM
authors.lastname: Elsherbiny
authors.affiliation: Program in Pharmaceutical Sciences, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Salama
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Mansoura, 35516, Egypt. Electronic address: emansaid@mans.edu.eg.
authors.forename: Eman
authors.initials: E
authors.lastname: Said
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Mansoura, 35516, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Sherbiny
authors.affiliation: 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.
authors.forename: Mohammed M H
authors.initials: MM
authors.lastname: Al-Gayyar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002338:Carotenoids / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000633:toxicity*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020107:Troponin T / Q000037:antagonists & inhibitors
chemical_list: D020107:Troponin T; D002338:Carotenoids; D004317:Doxorubicin; C029036:crocin; D002118:Calcium
keywords: Caspase-3; Crocin; Doxorubicin; Electrocardiogram; Interleukins; Tumor necrosis factor (TNF)-α