Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2024 , Vol 28 , Issue 3
Effects of lesinurad on HEK-293 human kidney cells: In vitro and molecular docking evaluation
Tugce BORAN1,Mahmoud ABUDAYYAK1,Mohammed T. QAOUD3
1Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey
2Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University-Cerrahpaşa, Istanbul, Turkey
3Department of Pharmacy, Faculty of Pharmacy, Cyprus International University, Nicosia, Northern Cyprus, Turkey
4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330. Etiler, Ankara, Turkey
DOI : 10.29228/jrp.733 Lesinurad is a drug used for the treatment of hyperuricemia. It has been reported that lesinurad causes renal adverse events. The molecular effects of lesinurad in the kidney cells have not been elucidated clearly. The embryonic kidney cells (HEK-293) were treated with lesinurad at various concentrations (12.5-100 μM) for 24h. The cytotoxicity, apoptotic effect, reactive oxygen species (ROS), lipid peroxidation (MDA), and total antioxidant capacity (TAC) levels were evaluated. Secretion of the inflammatory mediators was examined after lesinurad treatment. Additionally, molecular docking studies were performed for lesinurad with TNF-α and concanavalin a (ConA). Lesinurad did not induce apoptotic cell death at the tested concentrations. The ROS and MDA levels insignificantly declined, and the TAC level increased. TNF-α secretion was induced after 100 μM lesinurad treatment. Lesinurad significantly decreased the Con a-induced inflammatory mediators’ secretion. The docking studies results show a weak interaction with TNF-α but strong interaction with Con a proteins. These findings support that lesinuradinduced kidney toxicity could be related to the mechanical stress of uric acid crystals rather than the induction of inflammation by the initiation of oxidative damage. Keywords : Lesinurad-1; nephrotoxicity-2; inflammation-3; urate-lowering therapy -4; molecular docking-5
Marmara University