The Protective Effect of Apigenin on Myocardial Injury in Diabetic Rats mediating Activation of the PPAR-γ Pathway

Figures

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  Figure 1. Effect of apigenin on electrocardiogram (ECG) wave forms in streptozotocin (STZ)–isoproterenol-treated rats. The red arrows indicate the deformations of normal ECG waveforms at the place of formation of P-wave and red circle indicates the changes in the QRS complex, especially the ST segment. The green circle indicates the normalization of ECG waveforms and restoration of the ST segment, while the green arrows indicate the normal appearance of the ST segment and P-wave. *** p < 0.001 compared to diabetic isoproterenol; ### p < 0.001 compared to diabetic control; $ p < 0.001 compared to diabetic isoproterenol + apigenin.

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  Figure 2. Effects of apigenin on hemodynamic parameters in STZ–isoproterenol-treated rats. (A) Systolic arterial pressure (SAP); (B) Diastolic arterial pressure (DAP); (C) Mean arterial pressure (MAP); (D) Heart rate (HR). The data are expressed as mean ± standard error mea (SEM). The significance was determined by one-way ANOVA followed by the Bonferroni’s post hoc test: *** p < 0.001 as compared to diabetic isoproterenol; ### p < 0.001 as compared to diabetic control; $ p < 0.001 as compared to diabetic isoproterenol + apigenin. BPM: Beats per minute.

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  Figure 3. Effects of apigenin on peak positive and negative pressure development in STZ–isoproterenol-treated rats. (A) Left ventricular end diastolic pressure (LVEDP), (B) Maximal positive rate of left ventricular pressure (+LVdp/dtmax), (C) Maximal negative rate of left ventricular pressure (−LVdp/dtmin). The data are expressed as the mean ± SEM. The significance was determined by one-way ANOVA followed by the Bonferroni’s post hoc test: *** p < 0.001 compared to diabetic isoproterenol; ### p < 0.001 compared to diabetic control; $ p < 0.001 compared to diabetic isoproterenol + apigenin.

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  Figure 4. Effects of apigenin on cardiac injury markers in STZ–isoproterenol-treated rats. (A) Creatine kinase on myocardial bundle (CK-MB); (B) Lactate dehydrogenase (LDH). The data are expressed as mean ± SEM. The significance was determined by a one-way ANOVA followed by the Bonferroni’s post hoc test: *** p < 0.001 compared to diabetic isoproterenol; ### p < 0.001 compared to diabetic control; $ p < 0.001 compared to diabetic isoproterenol + apigenin (IU: International unit).

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  Figure 5. Effects of apigenin on oxidative stress in STZ–isoproterenol treated rats. (A) Malondialdehyde (MDA) content; (B) Glutathione (GSH); (C) Catalase; (D) Superoxide dismutase (SOD). The data are expressed as mean ± SEM. The significance was determined by one-way ANOVA followed by the Bonferroni’s post hoc test: *** p < 0.001 compared to diabetic isoproterenol; ### p < 0.001 compared to diabetic control; $ p < 0.001 compared to diabetic isoproterenol + apigenin.

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  Figure 6. Effects of apigenin on expression of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax) proteins and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in STZ–isoproterenol-treated rats. Immunohistochemical analysis of Bax (A1–E1) and Bcl-2 (A2–E2); TUNEL-positive cell (A3–E3; 20×; Scale bar: 100 µm) in various groups. (A1–A3): Diabetic control; (B1–B3): Diabetic isoproterenol; (C1–C3): Diabetic isoproterenol + apigenin; (D1–D3): Diabetic isoproterenol + GW9662 (E1–E3): Diabetic isoproterenol + GW9662 + apigenin.

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  Figure 7. Effects of apigenin on PPAR-γ expression in STZ–isoproterenol-treated rats quantified by Western blot analysis. The data are expressed as mean ± SEM. The significance was determined by one-way ANOVA followed by the Bonferroni’s post hoc test: *** p < 0.001 compared to diabetic isoproterenol; ### p < 0.001 compared to diabetic control; $ p < 0.001 compared to diabetic isoproterenol + GW9662 + apigenin.

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  Figure 8. Effect of apigenin on histopathology in STZ–isoproterenol treated rats. (A) Diabetic control; (B) Diabetic isoproterenol; (C) Diabetic isoproterenol + apigenin; (D) Diabetic isoproterenol + GW9662; (E) Diabetic isoproterenol + GW9662 + apigenin. Scale bar: 100 µm.