Cargando…

Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats

Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rod...

Descripción completa

Detalles Bibliográficos
Autores principales: Abdelzaher, Walaa Yehia, Ahmed, Sabreen Mahmoud, Welson, Nermeen N., Alsharif, Khalaf F., Batiha, Gaber El-Saber, Labib, Dina A. Aly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170324/
https://www.ncbi.nlm.nih.gov/pubmed/34093197
http://dx.doi.org/10.3389/fphar.2021.669679
_version_ 1783702218233348096
author Abdelzaher, Walaa Yehia
Ahmed, Sabreen Mahmoud
Welson, Nermeen N.
Alsharif, Khalaf F.
Batiha, Gaber El-Saber
Labib, Dina A. Aly
author_facet Abdelzaher, Walaa Yehia
Ahmed, Sabreen Mahmoud
Welson, Nermeen N.
Alsharif, Khalaf F.
Batiha, Gaber El-Saber
Labib, Dina A. Aly
author_sort Abdelzaher, Walaa Yehia
collection PubMed
description Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1β, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways.
format Online
Article
Text
id pubmed-8170324
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81703242021-06-03 Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats Abdelzaher, Walaa Yehia Ahmed, Sabreen Mahmoud Welson, Nermeen N. Alsharif, Khalaf F. Batiha, Gaber El-Saber Labib, Dina A. Aly Front Pharmacol Pharmacology Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1β, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways. Frontiers Media S.A. 2021-05-19 /pmc/articles/PMC8170324/ /pubmed/34093197 http://dx.doi.org/10.3389/fphar.2021.669679 Text en Copyright © 2021 Abdelzaher, Ahmed, Welson, Alsharif, Batiha and Labib. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Abdelzaher, Walaa Yehia
Ahmed, Sabreen Mahmoud
Welson, Nermeen N.
Alsharif, Khalaf F.
Batiha, Gaber El-Saber
Labib, Dina A. Aly
Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
title Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
title_full Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
title_fullStr Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
title_full_unstemmed Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
title_short Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
title_sort dapsone ameliorates isoproterenol-induced myocardial infarction via nrf2/ ho-1; tlr4/ tnf-α signaling pathways and the suppression of oxidative stress, inflammation, and apoptosis in rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170324/
https://www.ncbi.nlm.nih.gov/pubmed/34093197
http://dx.doi.org/10.3389/fphar.2021.669679
work_keys_str_mv AT abdelzaherwalaayehia dapsoneamelioratesisoproterenolinducedmyocardialinfarctionvianrf2ho1tlr4tnfasignalingpathwaysandthesuppressionofoxidativestressinflammationandapoptosisinrats
AT ahmedsabreenmahmoud dapsoneamelioratesisoproterenolinducedmyocardialinfarctionvianrf2ho1tlr4tnfasignalingpathwaysandthesuppressionofoxidativestressinflammationandapoptosisinrats
AT welsonnermeenn dapsoneamelioratesisoproterenolinducedmyocardialinfarctionvianrf2ho1tlr4tnfasignalingpathwaysandthesuppressionofoxidativestressinflammationandapoptosisinrats
AT alsharifkhalaff dapsoneamelioratesisoproterenolinducedmyocardialinfarctionvianrf2ho1tlr4tnfasignalingpathwaysandthesuppressionofoxidativestressinflammationandapoptosisinrats
AT batihagaberelsaber dapsoneamelioratesisoproterenolinducedmyocardialinfarctionvianrf2ho1tlr4tnfasignalingpathwaysandthesuppressionofoxidativestressinflammationandapoptosisinrats
AT labibdinaaaly dapsoneamelioratesisoproterenolinducedmyocardialinfarctionvianrf2ho1tlr4tnfasignalingpathwaysandthesuppressionofoxidativestressinflammationandapoptosisinrats