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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10144806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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