Cargando…

Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart

Background Cisplatin 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-d...

Descripción completa

Detalles Bibliográficos
Autores principales: Bukhari, Ishfaq A, Mohamed, Osama Y, Alhowikan, Abdulrahman M, Lateef, Rahmathunnisa, Hagar, Hanan, Assiri, Raghad A, Alqahtani, Wa’ad Massoud A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cureus 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866754/
https://www.ncbi.nlm.nih.gov/pubmed/35228931
http://dx.doi.org/10.7759/cureus.21572
_version_ 1784655901673652224
author Bukhari, Ishfaq A
Mohamed, Osama Y
Alhowikan, Abdulrahman M
Lateef, Rahmathunnisa
Hagar, Hanan
Assiri, Raghad A
Alqahtani, Wa’ad Massoud A
author_facet Bukhari, Ishfaq A
Mohamed, Osama Y
Alhowikan, Abdulrahman M
Lateef, Rahmathunnisa
Hagar, Hanan
Assiri, Raghad A
Alqahtani, Wa’ad Massoud A
author_sort Bukhari, Ishfaq A
collection PubMed
description Background Cisplatin 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. Methodology The 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. Results Cisplatin (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, cisplatin-induced reduction in glutathione and increased level of malondialdehyde in the myocardium was reversed by concurrent administration of rutin in isolated rat hearts. Conclusions Cisplatin 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.
format Online
Article
Text
id pubmed-8866754
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Cureus
record_format MEDLINE/PubMed
spelling pubmed-88667542022-02-27 Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart Bukhari, Ishfaq A Mohamed, Osama Y Alhowikan, Abdulrahman M Lateef, Rahmathunnisa Hagar, Hanan Assiri, Raghad A Alqahtani, Wa’ad Massoud A Cureus Preventive Medicine Background Cisplatin 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. Methodology The 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. Results Cisplatin (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, cisplatin-induced reduction in glutathione and increased level of malondialdehyde in the myocardium was reversed by concurrent administration of rutin in isolated rat hearts. Conclusions Cisplatin 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. Cureus 2022-01-24 /pmc/articles/PMC8866754/ /pubmed/35228931 http://dx.doi.org/10.7759/cureus.21572 Text en Copyright © 2022, Bukhari et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Preventive Medicine
Bukhari, Ishfaq A
Mohamed, Osama Y
Alhowikan, Abdulrahman M
Lateef, Rahmathunnisa
Hagar, Hanan
Assiri, Raghad A
Alqahtani, Wa’ad Massoud A
Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart
title Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart
title_full Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart
title_fullStr Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart
title_full_unstemmed Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart
title_short Protective Effect of Rutin Trihydrate Against Dose-Dependent, Cisplatin-Induced Cardiac Toxicity in Isolated Perfused Rat’s Heart
title_sort protective effect of rutin trihydrate against dose-dependent, cisplatin-induced cardiac toxicity in isolated perfused rat’s heart
topic Preventive Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866754/
https://www.ncbi.nlm.nih.gov/pubmed/35228931
http://dx.doi.org/10.7759/cureus.21572
work_keys_str_mv AT bukhariishfaqa protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart
AT mohamedosamay protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart
AT alhowikanabdulrahmanm protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart
AT lateefrahmathunnisa protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart
AT hagarhanan protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart
AT assiriraghada protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart
AT alqahtaniwaadmassouda protectiveeffectofrutintrihydrateagainstdosedependentcisplatininducedcardiactoxicityinisolatedperfusedratsheart