Saffron ( Crocus sativus ) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbi
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ORIGINAL PAPER
Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbit heart Moni Nader & Nathalie Chahine & Charelle Salem & Ramez Chahine
Received: 20 January 2016 / Accepted: 29 July 2016 # University of Navarra 2016
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 ischemiareperfusion (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
M. Nader Department of Physiological Sciences, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Kingdom of Saudi Arabia M. Nader Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia N. Chahine : C. Salem : R. Chahine (*) Physiology Laboratory, Faculty of Medical Sciences, and Doctoral School for Science and Technology, Lebanese University, Hadath, Lebanon e-mail: [email protected]
myocardium of S/IR hearts. Histological examination combined to biochemical analysis indicated that hearts preexposed 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. Keywords Saffron . Heart . Ischemia-reperfusion injuries . Reactive oxygen species
Introduction Myocardial ischemia (MI) is a reduced blood flow to cardiac muscle often caused by narrowing or complete blockade of the coronary arteries. Reperfusion (invasive or non-invasive interventions) remains the ultimate recourse to salvage the ischemic myocardium; however, it often engenders damage to the reperfused tissue owing to the excessive generation of reactive oxygen species (ROS) (reviewed in [46]). The detrimental effect of ROS on cell functio
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