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Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals

Cadmium (Cd) is a serious pollutant in the environment. Candesartan is an angiotensin II (Ang II) receptor antagonist with promising diverse health benefits. The current study is planned to investigate the hepatorenal protective effects of candesartan against Cd-induced hepatic and renal intoxicatio...

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Autores principales: Kamel, Esam O., Gad-Elrab, Wail M., Ahmed, Mohammed A., Mohammedsaleh, Zuhair M., Hassanein, Emad H. M., Ali, Fares E. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931870/
https://www.ncbi.nlm.nih.gov/pubmed/35590119
http://dx.doi.org/10.1007/s12011-022-03286-4
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author Kamel, Esam O.
Gad-Elrab, Wail M.
Ahmed, Mohammed A.
Mohammedsaleh, Zuhair M.
Hassanein, Emad H. M.
Ali, Fares E. M.
author_facet Kamel, Esam O.
Gad-Elrab, Wail M.
Ahmed, Mohammed A.
Mohammedsaleh, Zuhair M.
Hassanein, Emad H. M.
Ali, Fares E. M.
author_sort Kamel, Esam O.
collection PubMed
description Cadmium (Cd) is a serious pollutant in the environment. Candesartan is an angiotensin II (Ang II) receptor antagonist with promising diverse health benefits. The current study is planned to investigate the hepatorenal protective effects of candesartan against Cd-induced hepatic and renal intoxication. Our results demonstrated that candesartan effectively attenuated Cd-induced hepatorenal intoxication, as evidenced by improving hepatic and renal function biomarkers. Besides, candesartan reversed hepatic and renal histopathological abrasions induced by Cd toxicity. Candesartan antioxidant effect was mediated by Nrf2 activation. Also, candesartan suppressed hepatorenal inflammation by modulating NF-κB/IκB. Moreover, candesartan attenuated Cd hepatorenal apoptosis by upregulating Bcl-2 and downregulating Bax and Cyt-C proteins. Interestingly, these effects are suggested to be an outcome of modulating of Ang II/Ang 1–7 signal. Overall, our findings revealed that candesartan could attenuate Cd-induced hepatorenal intoxication through modulation of Nrf2, NF-κB/IκB, Bax/Bcl-2/Cyt-c, and Ang II/Ang 1–7 signaling pathways.
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spelling pubmed-99318702023-02-17 Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals Kamel, Esam O. Gad-Elrab, Wail M. Ahmed, Mohammed A. Mohammedsaleh, Zuhair M. Hassanein, Emad H. M. Ali, Fares E. M. Biol Trace Elem Res Article Cadmium (Cd) is a serious pollutant in the environment. Candesartan is an angiotensin II (Ang II) receptor antagonist with promising diverse health benefits. The current study is planned to investigate the hepatorenal protective effects of candesartan against Cd-induced hepatic and renal intoxication. Our results demonstrated that candesartan effectively attenuated Cd-induced hepatorenal intoxication, as evidenced by improving hepatic and renal function biomarkers. Besides, candesartan reversed hepatic and renal histopathological abrasions induced by Cd toxicity. Candesartan antioxidant effect was mediated by Nrf2 activation. Also, candesartan suppressed hepatorenal inflammation by modulating NF-κB/IκB. Moreover, candesartan attenuated Cd hepatorenal apoptosis by upregulating Bcl-2 and downregulating Bax and Cyt-C proteins. Interestingly, these effects are suggested to be an outcome of modulating of Ang II/Ang 1–7 signal. Overall, our findings revealed that candesartan could attenuate Cd-induced hepatorenal intoxication through modulation of Nrf2, NF-κB/IκB, Bax/Bcl-2/Cyt-c, and Ang II/Ang 1–7 signaling pathways. Springer US 2022-05-19 2023 /pmc/articles/PMC9931870/ /pubmed/35590119 http://dx.doi.org/10.1007/s12011-022-03286-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kamel, Esam O.
Gad-Elrab, Wail M.
Ahmed, Mohammed A.
Mohammedsaleh, Zuhair M.
Hassanein, Emad H. M.
Ali, Fares E. M.
Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals
title Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals
title_full Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals
title_fullStr Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals
title_full_unstemmed Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals
title_short Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals
title_sort candesartan protects against cadmium-induced hepatorenal syndrome by affecting nrf2, nf-κb, bax/bcl-2/cyt-c, and ang ii/ang 1–7 signals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931870/
https://www.ncbi.nlm.nih.gov/pubmed/35590119
http://dx.doi.org/10.1007/s12011-022-03286-4
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