The Protective Effects of Receptor-Interactive Protein Kinase-3 Inhibitor - Dabrafenib on Cisplatin Induced Nephrotoxicity

Objective: The aim of this study is to investigate the protective effects of dabrafenib, a receptor-interacting kinase-3 enzyme inhibitor, against necroptosis which has an important role in Cisplatin-induced nephrotoxicity. Methods: 32 male Sprague-Dawley rats were divided into 4 groups. A single dose of i.p. saline was given to the first group. In the second group, a single dose of cisplatin (5 mg/kg i.p.) was given. In the third group, 10mg/kg i.p injections of Dabrafenib began a day before injection of a single dose of 5 mg/kg, i.p. cisplatin for 7 days. In the forth group 10mg/kg Dabrafnib was injected i.p. for 7 days. After 7 days, in all groups rats were anesthetized and with a laparotomy left kidneys were isolated. Histopathological examinations, Western-Blot analyses (expression levels of RIP1, RIP3, and MLKL proteins), and malondialdehyde (MDA) measurements were performed on the isolated kidney tissues Results: In the biochemical evaluation of the study, it was observed that MDA levels in the kidney tissue increased significantly in the Cisplatin group compared to the control group (p