title: Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbit heart.
abstract: Restoration of blood flow to the ischemic myocardium is imperative to avoid demise of cardiomyocytes, but is paradoxically associated with irreversible damage to cardiac tissues due to the excessive generation of reactive oxygen species (ROS). We have previously reported that saffron, a natural antioxidant, attenuated ischemia-reperfusion (IR) injuries in vitro; however, its role in a meaningful cardiac recovery remains unknown. Here, we show that saffron supplement (oral administration for 6 weeks) reduced myocardial damage and restored cardiac function in an IR model of rabbit hearts. This was evidenced by improved left ventricle pressure, heart rate and coronary flow, and left ventricle end diastolic pressure (LVEDP) in IR hearts (isolated from rabbits pre-exposed to saffron (S/IR)). Electrophysiological recordings revealed a significant decline in both premature ventricle contraction and ventricle tachycardia/fibrillation in S/IR compared to IR hearts. This was paralleled by increased expression of the contractile proteins α-actinin and Troponin C in the myocardium of S/IR hearts. Histological examination combined to biochemical analysis indicated that hearts pre-exposed to saffron exhibited reduced infarct size, lower lipid peroxidation, with increased glutathione peroxidase activity, and oxidation of nitro blue tetrazolium (by reactive oxygen species). Furthermore, in contrast with IR hearts, saffron pretreatment induced restoration of the phosphorylation level of the survival proteins Akt and 4EBP1 and reduced activity of p38. Collectively, our data demonstrate that the natural antioxidant saffron plays a pivotal role in halting IR-associated cardiac injuries and emerges as a novel preventive tool for ischemic heart disease.
authors: Department of Physiological Sciences, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh, 11533, Kingdom of Saudi Arabia.|Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.
authors: Moni
authors: M
authors: Nader
authors: Physiology Laboratory, Faculty of Medical Sciences, and Doctoral School for Science and Technology, Lebanese University, Hadath, Lebanon.
authors: Nathalie
authors: N
authors: Chahine
authors: Physiology Laboratory, Faculty of Medical Sciences, and Doctoral School for Science and Technology, Lebanese University, Hadath, Lebanon.
authors: Charelle
authors: C
authors: Salem
authors: Physiology Laboratory, Faculty of Medical Sciences, and Doctoral School for Science and Technology, Lebanese University, Hadath, Lebanon. rmchahin@ul.edu.lb.
authors: Ramez
authors: R
authors: Chahine
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D027622:Crocus / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019209:Troponin C / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D019209:Troponin C; D000185:Actinin; D005979:Glutathione Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Heart; Ischemia-reperfusion injuries; Reactive oxygen species; Saffron