Quercetin attenuates ferroptosis-associated myocardial injury in rats after coronary microembolization by activating the Nrf2/HO-1 signaling pathway.

Figures

• 

  Figure 1. Quercetin improves cardiac function in rats after CME (A) Representative echocardiograms of each group. (B-E) LVEF, LVFS, LVEDd, and LVESd in each group of rats. The data were analyzed using one-way ANOVA with post hoc Fisher's LSD test and presented as mean±SD (n = 7). *P<0.05 vs Sham group; △P<0.05 vs CME group; #P<0.05 vs Que group LVEF: Left ventricular ejection fraction; LVFS: left ventricular fractional shortening; LVEDd: left ventricular end-diastolic diameter; LVESd: left ventricular end-systolic diameters

• 

  Figure 2. Quercetin reduces myocardial injury and ferroptosis marker levels in rats (A-E) Levels of serum cTnI, CK-MB, Fe2+, GSH, and MDA. Data are presented as the mean±SD (n=6). Statistical analyses for Figure 2A, Figure 2D, and Figure 2E were performed using one-way ANOVA followed by Dunnett's T3 post hoc test, while Figure 2B and Figure 2C were analyzed using one-way ANOVA followed by Fisher's LSD post hoc test. *P<0.05 vs Sham group; △P<0.05 vs CME group; #P<0.05 vs Que group cTnI: Cardiac troponin I; CK-MB: Creatine kinase MB isoenzyme; GSH: Glutathione; MDA: Malondialdehyde

• 

  Figure 3. Hematoxylin and Eosin (HE) and Heidenhain iron hematoxylin staining of rat tissue (A) HE staining. Microspheres with inflammatory cell infiltration were observed in the CME, Que, and Que+ML385 groups, but not in the sham surgery group. Black arrows indicate microspheres (×100 magnification; scale bar=100μm)(n=3). (B) Heidenhain iron hematoxylin staining. Ischemic myocardium is prominently displayed in brown-black. Red arrows indicate the area of microinfarction. (C) The microinfarct size in each group. The data were analyzed using one-way ANOVA with post hoc Fisher's LSD test and presented as mean±SD. *P<0.05 vs Sham group; △P<0.05 vs CME group; #P<0.05 vs Que group HE: Hematoxylin and eosin staining

• 

  Figure 4. (A-D) Changes in mRNA expression levels of Nrf2, HO-1, ACSL4, and Gpx4 across rat groups Data are presented as mean±SD (n=4). Statistical analyses for Figures 4A and 4C were performed using one-way ANOVA with Dunnett's T3 post hoc test, whereas Figures 4B and 4D were analyzed using one-way ANOVA with Fisher's LSD post hoc test. *P<0.05 vs Sham group; △P<0.05 vs CME group; #P<0.05 vs Que group Nrf2: Nuclear factor erythroid 2-related factor 2; HO-1: Heme oxygenase-1; ACSL4: Acyl-CoA synthetase long-chain family member 4; Gpx4: Glutathione peroxidase 4

• 

  Figure 5. Quercetin inhibits cardiomyocyte ferroptosis through the Nrf2/HO-1 signaling pathway in rats (A-F): Changes of relative expression levels of Nrf2, HO-1, ACSL4, Ferritin, and Gpx4 proteins in each group.The data were analyzed using one-way ANOVA with post hoc Fisher's LSD test and presented as mean±SD (n=4). *P<0.05 vs Sham group; △P<0.05 vs CME group; #P<0.05 vs Que group Nrf2: Nuclear factor erythroid 2-related factor 2; HO-1: Heme oxygenase-1; ACSL4: Acyl-CoA synthetase long-chain family member 4; Gpx4: Glutathione peroxidase 4

• 

  Figure 6. Subcellular localization and relative abundance of ACSL4 and GPX4 in rat myocardial tissue for each group (n=3) (A) Representative immunofluorescence images of ACSL4. (B) Representative immunofluorescence images of GPX4. Magnification,×200; Scale bar =100 μm ACSL4: Acyl-CoA synthetase long-chain family member 4; Gpx4: Glutathione peroxidase 4

• 

  Figure 7. Immunofluorescence images of Ferritin in rat myocardial tissue for each group (n=3) (A) Representative immunofluorescence images of Ferritin. Magnification,×200; Scale bar =100 μm. (B-D): The fluorescence intensity of ACSL4, Ferritin, and Gpx4 for each group. The data were analyzed using one-way ANOVA with post hoc Fisher's LSD test and presented as mean±SD (n=3). *P<0.05 vs Sham group; △P<0.05 vs CME group; #P<0.05 vs Que group ACSL4: Acyl-CoA synthetase long-chain family member 4; Gpx4: Glutathione peroxidase 4