Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.

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 FINDINGS: Diabetic rats underwent 30 minutes of is...

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Main Authors: Dongdong Sun, Jie Huang, Zheng Zhang, Haokao Gao, Jiayi Li, Min Shen, Feng Cao, Haichang Wang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3303839?pdf=render
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spelling doaj-7ee1af7f7bd74e4abe20309a364745952020-11-25T00:04:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3349110.1371/journal.pone.0033491Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.Dongdong SunJie HuangZheng ZhangHaokao GaoJiayi LiMin ShenFeng CaoHaichang WangBACKGROUND: 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 FINDINGS: Diabetic 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/SIGNIFICANCE: This 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.http://europepmc.org/articles/PMC3303839?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Dongdong Sun
Jie Huang
Zheng Zhang
Haokao Gao
Jiayi Li
Min Shen
Feng Cao
Haichang Wang
spellingShingle Dongdong Sun
Jie Huang
Zheng Zhang
Haokao Gao
Jiayi Li
Min Shen
Feng Cao
Haichang Wang
Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
PLoS ONE
author_facet Dongdong Sun
Jie Huang
Zheng Zhang
Haokao Gao
Jiayi Li
Min Shen
Feng Cao
Haichang Wang
author_sort Dongdong Sun
title Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
title_short Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
title_full Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
title_fullStr Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
title_full_unstemmed Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
title_sort luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description 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 FINDINGS: Diabetic 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/SIGNIFICANCE: This 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.
url http://europepmc.org/articles/PMC3303839?pdf=render
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