BackgroundProgranulin is an adipokine, encoded by the progranulin (GRN) gene. Progranulin is expressed in atherosclerosis, but its effects in cardiac ischemia and reperfusion injury are unknown. Therefore, this study aimed to investigate the effects of progranulin in a rat model of acute myocardial ischemia/reperfusion (MI/R) injury in vivo.Material/MethodsThe model of acute MI/R injury was established in male Wistar rats by ligation of the left anterior descending (LAD) coronary artery for 30 minutes and reperfusion for 60 minutes. Before modeling, one group was treated with progranulin (0.03 μg/kg), and one group was treated with the P13K/Akt inhibitor, LY294002 (3 mg/kg). Left ventricular function (LV) was monitored, including the LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and changes in LV pressure. At the end of the study, blood and myocardial tissue were examined. Cardiac biochemical markers, histopathology, gene expression, and apoptosis were analyzed.ResultsProgranulin improved cardiac function following acute MI/R injury and significantly improved recovery of cardiac contractility and LVSP. Progranulin significantly reduced myocyte apoptosis, inflammation, and tissue edema, and was highly expressed in cardiac tissue following MI/R injury. The cardioprotective effect of progranulin was reduced by blocking the P13K/Akt signaling pathway.ConclusionsIn the rat model of acute MI/R injury, progranulin had a protective effect on cardiac function and morphology, associated with activation of the P13K/Akt signaling pathway. The mechanisms of the anti-apoptotic, anti-inflammatory, and inotropic effects of progranulin in the setting of acute MI/R injury require further in vivo studies.
Background The present study aims to investigate the protective effect of rutin against cisplatin induced toxic effects on the mechanical performance of the myocardium, histopathology, and oxidative stress in isolated perfused rat hearts. Methods Cardiotoxicity of cisplatin was assessed at three dosage levels (1, 7, and 14 mg/l) in the isolated perfused rat hearts. The toxic effect of cisplarin was assessed on left ventricular pressure (LVP), heart rate (HR), dp/dt(max), dp/dt (min), perfusion pressure, pressure-time index, contractility index and duration of diastole. Measurements were carried out one minute before perfusion of cisplatin and 60 minutes after perfusion. Results Cisplatin reduced significantly (p < 0.05) in a dose-dependent manner LVP, dp/dt(max), dp/dt(min) and pressure- time index. Perfusion of rutin trihydrate (1 µM/l), 10 minutes before administration of cisplatin and throughout the experiment significantly (p < 0.05) attenuated the detrimental effects of cisplatin on cardiac parameters. Cisplatin caused degeneration and necrosis of cardiac muscle cells, while rutin reduced these changes and restored normal heart histology. Moreover, cisplatin reduced the myocardium concentration of reduced glutathione and increased the level of malondialdehyde, whereas rutin almost reversed these changes. Conclusion Cisplatin-induced dose-dependent impairment of several parameters of cardiac function and produced histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were ameliorated by rutin trihydrate. These findings suggest the potential protective effects of rutin trihydrate against cisplatin-induced cardiotoxicity.
BackgroundCisplatin is a common anticancer drug with potential cardiac and renal toxicities. Rutin, a natural compound present in various medicinal plants, has been shown to protect against chemotherapy-induced toxicities. In this study, we explored the protective effect of rutin against the dose-dependent cardiotoxic effects of cisplatin such as perfusion pressure, histopathologic effect on the myocardium, and oxidative stress in isolated perfused rat hearts. MethodologyThe cardiotoxic effects of cisplatin were studied at three dosages (1, 7, and 14 mg/L) in isolated perfused rat hearts. The dose-dependent, cisplatin-induced toxic effects on left ventricular pressure (LVP), heart rate (HR), dp/dt (maximum), dp/dt (minimum), perfusion pressure, pressure-time index, contractility index, and duration of diastole were assessed. The effects of cisplatin were measured one minute before perfusion of cisplatin and 60 minutes after perfusion of the isolated rat hearts. ResultsCisplatin (1-14 mg/L) caused a significant (p < 0.05) dose-dependent reduction in LVP. The percentage LVP values reduced from 94 ± 9 (control untreated hearts) to 70 ± 6, 69 ± 5, and 65 ± 4 in hearts treated with 1, 7, and 14 mg/L of cisplatin, respectively. Similarly, cisplatin at similar doses caused a marked reduction in the values of dp/dt (maximum), dp/dt (minimum), and pressure-time index in isolated rat hearts. The respective percentage values of these parameters compared to those of untreated hearts were significantly reduced from 101 ± 7 to 72 ± 5, 92 ± 8 to 69 ± 4, and 92 ± 12 to 57 ± 7 in hearts treated with 14 mg/L of cisplatin. Perfusion of hearts with rutin trihydrate (1 µM/L) 10 minutes before administration of cisplatin and throughout the experiment attenuated the detrimental effects of cisplatin on cardiac functions in isolated rat hearts (p < 0.05). In addition, cisplatin-induced degeneration and necrosis of cardiac muscle cells reduced with the concurrent administration of rutin and restored normal heart histology. Moreover, cisplatininduced reduction in glutathione and increased level of malondialdehyde in the myocardium was reversed by concurrent administration of rutin in isolated rat hearts. ConclusionsCisplatin produced a dose-dependent impairment of several parameters of cardiac function such as LVP, contractility index, and pressure-time index. It caused histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were suppressed by rutin trihydrate, suggesting the potential protective effects of rutin against cisplatin-induced cardiotoxicity. Rutin trihydrate also improved the reduced glutathione contents and suppressed the malondialdehyde contents in the cardiac tissue of isolated rat hearts, suggesting that the observed beneficial effects of rutin trihydrate in this study could be related to its antioxidant properties.
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