Protective effect of dapagliflozin against cyclosporine A-induced nephrotoxicity.

Autor: Deger M; Department of Urology, Faculty of Medicine, Çukurova University, Adana, Turkey., Kaya B; Department of Nephrology, Faculty of Medicine, Çukurova University, Adana, Turkey., Akdogan N; Department of Urology, Faculty of Medicine, Çukurova University, Adana, Turkey., Kaplan HM; Department of Pharmacology, Faculty of Medicine, Cukurova University, Adana, Turkey., Bagir E; Department of Pathology, Faculty of Medicine, Çukurova University, Adana, Turkey., Izol V; Department of Urology, Faculty of Medicine, Çukurova University, Adana, Turkey., Aridogan IA; Department of Urology, Faculty of Medicine, Çukurova University, Adana, Turkey.
Jazyk: angličtina
Zdroj: Drug and chemical toxicology [Drug Chem Toxicol] 2022 Nov; Vol. 45 (6), pp. 2637-2643. Date of Electronic Publication: 2021 Sep 27.
DOI: 10.1080/01480545.2021.1979996
Abstrakt: This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an eight-week-old Balb\c albino strain were divided into four groups: control group, CsA group, DAPA group, and CsA + DAPA group. On day 9 of treatment, the animals were decapitated, and bilateral nephrectomy was performed. Oxidative stress and apoptosis were evaluated with caspase-3 activity, total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), myeloperoxidase (MPO), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the right kidney resection material. The left kidney resection material was evaluated histopathologically. CsA increased caspase-3 activity, Bax, TOS, MDA, TAS, and MPO levels, and the administration of DAPA with CsA significantly reduced this increase in levels ( p  < 0.001, p  < 0.001, p  < 0.001, p  < 0.001, p  < 0.001, and p  < 0.001, respectively). CsA decreased Bcl-2 levels, and administration of CsA + DAPA significantly increased Bcl-2 levels compared with only CsA administration ( p  < 0.001). Additionally, administration of DAPA significantly reduced the histopathological findings (parenchymal inflammation, hyaline cast formation, vacuolization, and lysis of renal tubular cells) caused by CsA. DAPA reduces oxidative stress, apoptosis, and histopathological damage caused by CsA in renal tissue.
Databáze: MEDLINE
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