Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation
Mohamed El-Sherbiny,
Mohamed El-Shafey,
Eman Said,
Gehan Ahmed Shaker,
Mohamed El-Dosoky,
Hasnaa Ali Ebrahim,
Sally Yussef Abed,
Khalid M. Ibraheem,
Ahmed Mohsen Faheem,
Muntazar AlMutawa,
Bayader Alatawi,
Nehal M. Elsherbiny
Affiliations
Mohamed El-Sherbiny
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Mohamed El-Shafey
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Eman Said
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
Gehan Ahmed Shaker
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Mohamed El-Dosoky
Department of Neuroscience Technology, College of Applied Medical Science in Jubail, Imam Abdulrahman Bin Faisal University, Jubail 34221, Saudi Arabia
Hasnaa Ali Ebrahim
Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
Sally Yussef Abed
Department of Respiratory Care, College of Applied Medical Science in Jubail, Imam Abdulrahman Bin Faisal University, Jubail 35811, Saudi Arabia
Khalid M. Ibraheem
Department of Anaesthesia Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman Bin Faisal University, Jubail 35811, Saudi Arabia
Ahmed Mohsen Faheem
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Muntazar AlMutawa
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Bayader Alatawi
PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
Nehal M. Elsherbiny
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
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.
