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