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Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of...

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Autores principales: El-Sherbiny, Mohamed, El-Shafey, Mohamed, Said, Eman, Shaker, Gehan Ahmed, El-Dosoky, Mohamed, Ebrahim, Hasnaa Ali, Abed, Sally Yussef, Ibraheem, Khalid M., Mohsen Faheem, Ahmed, AlMutawa, Muntazar, Alatawi, Bayader, Elsherbiny, Nehal M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144980/
https://www.ncbi.nlm.nih.gov/pubmed/35629430
http://dx.doi.org/10.3390/life12050764
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author El-Sherbiny, Mohamed
El-Shafey, Mohamed
Said, Eman
Shaker, Gehan Ahmed
El-Dosoky, Mohamed
Ebrahim, Hasnaa Ali
Abed, Sally Yussef
Ibraheem, Khalid M.
Mohsen Faheem, Ahmed
AlMutawa, Muntazar
Alatawi, Bayader
Elsherbiny, Nehal M.
author_facet El-Sherbiny, Mohamed
El-Shafey, Mohamed
Said, Eman
Shaker, Gehan Ahmed
El-Dosoky, Mohamed
Ebrahim, Hasnaa Ali
Abed, Sally Yussef
Ibraheem, Khalid M.
Mohsen Faheem, Ahmed
AlMutawa, Muntazar
Alatawi, Bayader
Elsherbiny, Nehal M.
author_sort El-Sherbiny, Mohamed
collection PubMed
description In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury.
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spelling pubmed-91449802022-05-29 Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation El-Sherbiny, Mohamed El-Shafey, Mohamed Said, Eman Shaker, Gehan Ahmed El-Dosoky, Mohamed Ebrahim, Hasnaa Ali Abed, Sally Yussef Ibraheem, Khalid M. Mohsen Faheem, Ahmed AlMutawa, Muntazar Alatawi, Bayader Elsherbiny, Nehal M. Life (Basel) Article In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury. MDPI 2022-05-21 /pmc/articles/PMC9144980/ /pubmed/35629430 http://dx.doi.org/10.3390/life12050764 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
El-Sherbiny, Mohamed
El-Shafey, Mohamed
Said, Eman
Shaker, Gehan Ahmed
El-Dosoky, Mohamed
Ebrahim, Hasnaa Ali
Abed, Sally Yussef
Ibraheem, Khalid M.
Mohsen Faheem, Ahmed
AlMutawa, Muntazar
Alatawi, Bayader
Elsherbiny, Nehal M.
Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
title Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
title_full Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
title_fullStr Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
title_full_unstemmed Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
title_short Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
title_sort dapagliflozin, liraglutide, and their combination attenuate diabetes mellitus-associated hepato-renal injury—insight into oxidative injury/inflammation/apoptosis modulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144980/
https://www.ncbi.nlm.nih.gov/pubmed/35629430
http://dx.doi.org/10.3390/life12050764
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