FINERENONE MITIGATES CISPLATIN-INDUCED NEPHROTOXICITY ASSOCIATED WITH SUPPRESSION OF NOX4/FERROPTOSIS AND NLRP3 INFLAMMASOME PATHWAYS IN RATS

Cisplatin is a widely used chemotherapeutic agent whose clinical utility is limited by dose-dependent nephrotoxicity involving oxidative stress, ferroptosis, and inflammasome activation. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist used in diabetic kidney disease, has, to our knowledge, not previously been tested in chemotherapy-induced kidney injury. Forty-eight adult male Wistar rats were assigned to six groups (n = 8 each): control, cisplatin (7.5 mg/kg, single intraperitoneal dose), finerenone alone (5 or 10 mg/kg/day, oral, 10 days), and cisplatin combined with each finerenone dose. Renal function, oxidative stress, ferroptosis-related markers, NLRP3 inflammasome-related markers, cytokines, apoptosis-related markers, and Nrf2/HO-1 expression were assessed 72 hours after cisplatin administration. Cisplatin produced marked renal dysfunction, oxidative injury, and changes in ferroptosis-, inflammasome-, and apoptosis-related markers relative to control. Finerenone co-administration attenuated these changes in a dose-dependent manner, with the high dose reducing serum creatinine by approximately 54% relative to cisplatin alone, and increased Nrf2 and HO-1 mRNA expression. Finerenone alone did not affect renal function markers. These findings indicate that finerenone confers dose-dependent nephroprotection against cisplatin-induced kidney injury in rats. This protection was associated with changes consistent with suppression of the NOX4-associated ferroptosis pathway and NLRP3 inflammasome activation, and with increased Nrf2/HO-1 mRNA expression, supporting further evaluation of finerenone as a candidate nephroprotective agent.