Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca2+ Pathway

Figures

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  Figure 1. The ECG examination in different treated groups. (a): The electrocardiographic effect of FLP in different doses on ISO-induced MI in rats. (b): ECG in experimental rats pretreated with FLP (15, 30, and 45 mg/kg) in an ISO-induced MI model on HR, QT interval, R amplitude, and ST segment amplitude. (A) Normal group, (B) Iso group, (C) FLB 15 mg + Iso group, (D) FLB 30 mg + Iso group and FLB 45 mg + Iso group. Bars with different letters are significantly different according to DMRT at p < 0.001 level (n = 5). Data are expressed as Mean ± SD. ECG = electrocardiogram, FLP = flibanserin, ISO = isoproterenol, MI = myocardial infarction, HR = heart rate, DMRT = Duncan’s multiple range test.

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  Figure 2. Histopathological examination in the different treated groups. (A): Photomicrograph for specimens from the heart stained with H&E 10× & 40× in different treated groups. In the normal group: [H&E 10×] shows Compact, uniformly arranged myocardial fibers (Black arrows), [H&E 40×] myocytes show preserved uniform nuclei (Black arrows) and cytoplasmic cross striation (Red arrows). In ISO group: [H&E 10×] shows a wide separation of myocardial fibers due to interstitial edema (Black arrows), areas of myocardial fibers loss of eosinophilic staining and becoming pallor in appearance (Arrowheads), the influx of inflammatory cells into myocardial fibers (Red arrows), [H&E 40×] shows pathological changes of MI, interstitial edema between myocardial fibers (Black arrows), loss of cytoplasmic striation of myocytes with shrinkage of nuclei and prominence of the cell membrane (Arrowheads), some myocytes show an absence of nuclei (Yellow arrows), the influx of macrophages, indicating an inflammatory response to remove dead fibers (Red arrows). In FLP (15 mg/kg) + ISO group: [H&E 10×] shows no significant difference when compared to the ISO group as there is still a wide separation of myocardial…

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  Figure 3. Serum cardiac enzymes levels in experimental rats pretreated with FLP (15, 30, and 45 mg/kg) in an ISO-induced MI model (A): The cardiac serum level of Tnl (B): The cardiac serum level of CK-MB, (C): The cardiac serum level of LDH. (D): The cardiac serum level of CK. Bars with different letters are significantly different according to DMRT at p < 0.001 level (n = 5). Data are expressed as Mean ± SD. FLP = flibanserin, ISO = isoproterenol, MI = myocardial infarction, Tnl = troponin I, CK-MB = creatinine kinase-MB, LDH = lactate dehydrogenase, CK = creatine kinase, DMRT = Duncan’s multiple range test.

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  Figure 4. Effect of FLP in different doses on heart tissue level of GSH and MDA. (A): Heart level of GSH in experimental rats pretreated with FLP (15, 30, and 45 mg/kg) in an ISO-induced MI model. (B) Heart level of MDA in experimental rats pretreated with FLP (15, 30, and 45 mg/kg) in an ISO-induced MI model. Bars with different letters are significantly different according to DMRT at p < 0.001 level (n = 5). Data are expressed as Mean ± SD. FLP = flibanserin, GSH = reduced glutathione, MDA = malondialdehyde, ISO = isoproterenol, DMRT = Duncan’s multiple range test.

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  Figure 5. Proposed FLP action on DA, NE, and 5-HT centers of the brain. The figure represents the dopaminergic system (A) before and (B) after the administration of flibanserin. While noradrenergic system (C) before and (D) after administration of flibanserin. Finally, serotonergic system (E) before and (F) after administration of flibanserin. Glu = Glutamate, GABA = Gamma-aminobutyric acid, NE = Norepinephrine, DA = Dopamine, 5-HT = Serotonin, FLP = Flibanserin.