TY - JOUR
T1 - Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbit heart
AU - Nader, Moni
AU - Chahine, Nathalie
AU - Salem, Charelle
AU - Chahine, Ramez
N1 - Funding Information:
This work was supported by a research grant to RC from the research committee of Lebanese University. MN is a recipient of a KACST grant (no.13-BIO1452-20).
Publisher Copyright:
© 2016, University of Navarra.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Heart
KW - Ischemia-reperfusion injuries
KW - Reactive oxygen species
KW - Saffron
UR - http://www.scopus.com/inward/record.url?scp=84981266923&partnerID=8YFLogxK
U2 - 10.1007/s13105-016-0510-8
DO - 10.1007/s13105-016-0510-8
M3 - Article
C2 - 27507116
AN - SCOPUS:84981266923
SN - 1138-7548
VL - 72
SP - 711
EP - 719
JO - Journal of Physiology and Biochemistry
JF - Journal of Physiology and Biochemistry
IS - 4
ER -