Cargando…

Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways

Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition...

Descripción completa

Detalles Bibliográficos
Autores principales: Fawzy, Michael A., Maher, Sherif A., El-Rehany, Mahmoud A., Welson, Nermeen N., Albezrah, Nisreen K. A., Batiha, Gaber El-Saber, Fathy, Moustafa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879001/
https://www.ncbi.nlm.nih.gov/pubmed/35209172
http://dx.doi.org/10.3390/molecules27041383
_version_ 1784658794237657088
author Fawzy, Michael A.
Maher, Sherif A.
El-Rehany, Mahmoud A.
Welson, Nermeen N.
Albezrah, Nisreen K. A.
Batiha, Gaber El-Saber
Fathy, Moustafa
author_facet Fawzy, Michael A.
Maher, Sherif A.
El-Rehany, Mahmoud A.
Welson, Nermeen N.
Albezrah, Nisreen K. A.
Batiha, Gaber El-Saber
Fathy, Moustafa
author_sort Fawzy, Michael A.
collection PubMed
description Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the Bcl-2 gene and upregulated the Bax gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines’ levels, and suppression of the MAPK (ERK1/2, JNK, p38)–NF-κB intracellular signaling pathway.
format Online
Article
Text
id pubmed-8879001
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88790012022-02-26 Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways Fawzy, Michael A. Maher, Sherif A. El-Rehany, Mahmoud A. Welson, Nermeen N. Albezrah, Nisreen K. A. Batiha, Gaber El-Saber Fathy, Moustafa Molecules Article Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the Bcl-2 gene and upregulated the Bax gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines’ levels, and suppression of the MAPK (ERK1/2, JNK, p38)–NF-κB intracellular signaling pathway. MDPI 2022-02-18 /pmc/articles/PMC8879001/ /pubmed/35209172 http://dx.doi.org/10.3390/molecules27041383 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fawzy, Michael A.
Maher, Sherif A.
El-Rehany, Mahmoud A.
Welson, Nermeen N.
Albezrah, Nisreen K. A.
Batiha, Gaber El-Saber
Fathy, Moustafa
Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
title Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
title_full Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
title_fullStr Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
title_full_unstemmed Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
title_short Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways
title_sort vincamine modulates the effect of pantoprazole in renal ischemia/reperfusion injury by attenuating mapk and apoptosis signaling pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879001/
https://www.ncbi.nlm.nih.gov/pubmed/35209172
http://dx.doi.org/10.3390/molecules27041383
work_keys_str_mv AT fawzymichaela vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways
AT mahersherifa vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways
AT elrehanymahmouda vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways
AT welsonnermeenn vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways
AT albezrahnisreenka vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways
AT batihagaberelsaber vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways
AT fathymoustafa vincaminemodulatestheeffectofpantoprazoleinrenalischemiareperfusioninjurybyattenuatingmapkandapoptosissignalingpathways