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

Abstract

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.

Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats

“…Recent studies have shown potential for its use in situations where inflammation, oxidative stress, and apoptosis are present. Several authors have shown reduced lipid peroxidation, reduced NFκB, TNF-α, IL-1, IL-6, nitrous oxide production, apoptosis, and cardiac collagen deposition with the use of GLP-1 analogues in some experimental models of disease [ 9 , 10 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. In our study, we investigated the role of liraglutide on doxorubicin-induced cardiac toxicity.…”

Effect of Silver Nanoparticles With Thermoplastic Polyurethane on Postoperative Rehabilitation of Diabetic Patients With Open Fracture of Lower Extremities

“…However, in this study, we did not set up a blank control group using the TPU membrane alone, and prospective observation was lacking, which may offset the results. In addition, the safety of TPU/NS dressings should be evaluated by determining the liver and kidney function in diabetic patients with open fractures of lower extremities, as well as serum deposition because hepatocellular damage and nephropathy were associated with diabetes ( 32 ). Furthermore, the wound-healing rate would be assessed in the future to validate our clinical results.…”