Abstract
Background The present study was to investigate the effects and mechanism of Luteolin on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in diabetic rats with myocardial ischemia/reperfusion (I/R) injury.Methodology/Principal FindingsDiabetic rats underwent 30 minutes of ischemia followed by 3 h of reperfusion. Animals were pretreated with or without Luteolin before coronary artery ligation. The severity of myocardial I/R induced LDH release, arrhythmia, infarct size, cardiac function impairment, cardiomyocyte apoptosis were compared. Western blot analysis was performed to elucidate the target proteins of Luteolin. The inflammatory cytokine production were also examined in ischemic myocardium underwent I/R injury. Our results revealed that Luteolin administration significantly reduced LDH release, decreased the incidence of arrhythmia, attenuated myocardial infarct size, enhanced left ventricular ejection fraction and decreased myocardial apoptotic death compared with I/R group. Western blot analysis showed that Luteolin treatment up-regulated anti-apoptotic proteins FGFR2 and LIF expression, increased BAD phosphorylation while decreased the ratio of Bax to Bcl-2. Luteolin treatment also inhibited MPO expression and inflammatory cytokine production including IL-6, IL-1a and TNF-a. Moreover, co-administration of wortmannin and Luteolin abolished the beneficial effects of Luteolin.Conclusions/SignificanceThis study indicates that Luteolin preserves cardiac function, reduces infarct size and cardiomyocyte apoptotic rate after I/R injury in diabetic rats. Luteolin exerts its action by up-regulating of anti-apoptotic proteins FGFR2 and LIF expression, activating PI3K/Akt pathway while increasing BAD phosphorylation and decreasing ratio of Bax to Bcl-2.
Highlights
The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among patients with diabetes [1]
Luteolin administration significantly decreased the release of lactate dehydrogenase (LDH), a biochemical marker for necrotic cell death, as compared with the I/R group (116.6619.9 vs 161.6612.1, P = 0.003)
Luteolin significantly decreased the incidence of Premature ventricular beats (PVB) (33.3% vs 70%, P = 0.009), ventricular tachycardia (VT) (16.7% vs 50%, P = 0.013) and ventricular fibrillation (VF) (3.3% vs 30%, P = 0.012) as compared with the I/R group
Summary
The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among patients with diabetes [1]. Our previous study has shown that diabetes renders the heart more sensitive to I/R injury [3]. This warrants the significance of aggressive primary prevention against ischemia/reperfusion (I/R) injury in diabetic patients. Akt is known to regulate many survival pathways of the cardiac cells. It has been reported that PI3K/Akt pathway regulates cardiac contractility and cardiomyocyte apoptosis [12]. Activation of PI3K/Akt pathway is an effective way to reduce cardiomyocyte apoptosis reduces cardiac I/R injury. The present study was to investigate the effects and mechanism of Luteolin on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in diabetic rats with myocardial ischemia/reperfusion (I/R) injury
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
