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Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk

Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to sti...

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Autores principales: Taha, Medhat, Elazab, Sara T., Baokbah, Tourki A. S., Al-Kushi, Abdullah G., Mahmoud, Mohamed Ezzat, Abdelbagi, Omer, Qusty, Naeem F., El-Shenbaby, Ibrahim, Babateen, Omar, Badawy, Alaa. M., Ibrahim, Mohie Mahmoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144806/
https://www.ncbi.nlm.nih.gov/pubmed/37112604
http://dx.doi.org/10.3390/toxics11040377
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author Taha, Medhat
Elazab, Sara T.
Baokbah, Tourki A. S.
Al-Kushi, Abdullah G.
Mahmoud, Mohamed Ezzat
Abdelbagi, Omer
Qusty, Naeem F.
El-Shenbaby, Ibrahim
Babateen, Omar
Badawy, Alaa. M.
Ibrahim, Mohie Mahmoud
author_facet Taha, Medhat
Elazab, Sara T.
Baokbah, Tourki A. S.
Al-Kushi, Abdullah G.
Mahmoud, Mohamed Ezzat
Abdelbagi, Omer
Qusty, Naeem F.
El-Shenbaby, Ibrahim
Babateen, Omar
Badawy, Alaa. M.
Ibrahim, Mohie Mahmoud
author_sort Taha, Medhat
collection PubMed
description Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway.
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spelling pubmed-101448062023-04-29 Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk Taha, Medhat Elazab, Sara T. Baokbah, Tourki A. S. Al-Kushi, Abdullah G. Mahmoud, Mohamed Ezzat Abdelbagi, Omer Qusty, Naeem F. El-Shenbaby, Ibrahim Babateen, Omar Badawy, Alaa. M. Ibrahim, Mohie Mahmoud Toxics Article Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway. MDPI 2023-04-16 /pmc/articles/PMC10144806/ /pubmed/37112604 http://dx.doi.org/10.3390/toxics11040377 Text en © 2023 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
Taha, Medhat
Elazab, Sara T.
Baokbah, Tourki A. S.
Al-Kushi, Abdullah G.
Mahmoud, Mohamed Ezzat
Abdelbagi, Omer
Qusty, Naeem F.
El-Shenbaby, Ibrahim
Babateen, Omar
Badawy, Alaa. M.
Ibrahim, Mohie Mahmoud
Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
title Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
title_full Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
title_fullStr Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
title_full_unstemmed Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
title_short Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk
title_sort palliative role of zamzam water against cyclosporine-induced nephrotoxicity through modulating autophagy and apoptosis crosstalk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144806/
https://www.ncbi.nlm.nih.gov/pubmed/37112604
http://dx.doi.org/10.3390/toxics11040377
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