Qassim University
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Item Restricted Role of ADAM10/RXR-alpha/PAR-2/p-AKT Pathway in the Initiation of Acute Renal Failure(Saudi Digital Library, 2023-11-29) Aldakhili, Anas Sulaiman A; عبدالباقي، محمد صادق محمدAcute renal failure (ARF) is a harmful disease with high cost and mortality. The current work aims to compare the prophylactic effect of Fondaparinux (Fund) and the treatment effect of Alteplase (Alt) against ARF induced by cisplatin (Cis). Male sixty Balb/c mice were randomly distributed into six groups: Control, Cis, Alt, Fund, Cis + Fund, and Cis + Alt. Cis receiving groups administered Cis (30 mg/kg, i.p) on the 7 day. Mice groups of Fund and Fund + Cis administered Fund (5 mg/kg, i.p) for ten days. In the Alt and Alt + Cis groups, mice received Alteplase (0.9 mg.kg-1, i.v.) on the 7th day, six hours post-CP injection. At the end of the experiment (10 days), mice were euthanized. Group of Fund + Cis demonstrated significant retinoid X receptor alpha (RXR-α) elevation, platelet count, and phosphorylated Akt (p-Akt). Whereas a reduction in urea, uric acid, blood urea nitrogen (BUN), red blood cells (RBCs), white blood cells (WBCs), kidney injury score, prothrombin (PT), glucose levels and decreased relative kidney body weight, extracellular matrix deposition, protease-activated receptor 2 (PAR-2), A Disintegrin And Metalloproteinases-10 (ADAM10) and the expression of fibrinogen when compared to Cis-treated group. On the other hand, Cis + Alt treated mice exhibited expression of caspase-3 and reduction in levels of urea, uric acid, glucose, BUN, WBCs, RBCs, platelet count, and the expression of PT with a marked decrease in the expression of PAR-2 protein in comparison to Cis group. Creatinine levels for Cis + Alt or Fund + Cis treated mice showed comparable effects compared to the Cis- treated mice group. The findings of the current work revealed that the activation of the coagulation system in the form of increased fibrinogen and PAR-2 as a result of induction of ADAM10 in Cis- treatment mediates apoptosis in the form of increased expression of caspase 3 through p-Akt signaling. This effect is associated with RXR-α loss from proximal and distal tubules as lipid droplets. Pre-treating mice with the anticoagulant, Fund, resulting in improved all harmful effect and halted caused by Cis while the fibrinolytic agent, Alt, often failed to stop Cis-resulted effects.29 0