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

Sun D, Huang J, Zhang Z, Gao H, Li J, Shen M, Cao F, Wang H - PLoS ONE (2012)

Bottom Line: 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.Moreover, co-administration of wortmannin and Luteolin abolished the beneficial effects of Luteolin.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. wintersun3@gmail.com

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 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.

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Luteolin alleviates leukocyte infiltration and reduces cytokine levels after I/R injury in diabetic rats.Luteolin reduced the MPO activity compared with the I/R group and the wortmannin group (a). Luteolin reduced the levels of IL-6, IL-1α and TNF-α production compared with the I/R group and the wortmannin group (b, c, d). The columns and errors bars represent means and SD. *p<0.05 vs Non-DM, #p<0.05 vs Sham, §p<0.05 vs Luteolin.
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pone-0033491-g006: Luteolin alleviates leukocyte infiltration and reduces cytokine levels after I/R injury in diabetic rats.Luteolin reduced the MPO activity compared with the I/R group and the wortmannin group (a). Luteolin reduced the levels of IL-6, IL-1α and TNF-α production compared with the I/R group and the wortmannin group (b, c, d). The columns and errors bars represent means and SD. *p<0.05 vs Non-DM, #p<0.05 vs Sham, §p<0.05 vs Luteolin.

Mentions: MPO activity was increased in the diabetic group as compared with the non-diabetic group. Following 3 h of reperfusion, the activity of MPO was significantly elevated in the I/R group when compared to the sham group (25.4±3.5 vs 8.4±0.6 U/100 mg, P<0.001). Treatment with Luteolin reduced the MPO activity compared with the I/R group (18.3±1.6 vs 25.4±3.5 U/100 mg, P = 0.003) and the wortmannin group (18.3±1.6 vs 22.1±2.3 U/100 mg, P = 0.016) (Figure 6a).


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

Sun D, Huang J, Zhang Z, Gao H, Li J, Shen M, Cao F, Wang H - PLoS ONE (2012)

Luteolin alleviates leukocyte infiltration and reduces cytokine levels after I/R injury in diabetic rats.Luteolin reduced the MPO activity compared with the I/R group and the wortmannin group (a). Luteolin reduced the levels of IL-6, IL-1α and TNF-α production compared with the I/R group and the wortmannin group (b, c, d). The columns and errors bars represent means and SD. *p<0.05 vs Non-DM, #p<0.05 vs Sham, §p<0.05 vs Luteolin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303839&req=5

pone-0033491-g006: Luteolin alleviates leukocyte infiltration and reduces cytokine levels after I/R injury in diabetic rats.Luteolin reduced the MPO activity compared with the I/R group and the wortmannin group (a). Luteolin reduced the levels of IL-6, IL-1α and TNF-α production compared with the I/R group and the wortmannin group (b, c, d). The columns and errors bars represent means and SD. *p<0.05 vs Non-DM, #p<0.05 vs Sham, §p<0.05 vs Luteolin.
Mentions: MPO activity was increased in the diabetic group as compared with the non-diabetic group. Following 3 h of reperfusion, the activity of MPO was significantly elevated in the I/R group when compared to the sham group (25.4±3.5 vs 8.4±0.6 U/100 mg, P<0.001). Treatment with Luteolin reduced the MPO activity compared with the I/R group (18.3±1.6 vs 25.4±3.5 U/100 mg, P = 0.003) and the wortmannin group (18.3±1.6 vs 22.1±2.3 U/100 mg, P = 0.016) (Figure 6a).

Bottom Line: 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.Moreover, co-administration of wortmannin and Luteolin abolished the beneficial effects of Luteolin.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. wintersun3@gmail.com

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 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.

Show MeSH
Related in: MedlinePlus