INTRODUCTION
Cisplatin (CIS) is an antineoplastic agent used to treat various types of cancer, including testicular, ovarian, bladder, and lung cancer [1]. However, its use is limited due to its cumulative and dose-dependent toxic effects, such as nephrotoxicity, neurotoxicity, and ototoxicity [2]. CIS is known to accumulate significantly in the kidneys, particularly in the proximal tubules, with the S3 segment being the most affected [3]. The cellular pathology of nephrotoxicity is mediated by oxidative stress, apoptosis, inflammation, and fibrogenesis [4]. CIS-mediated oxidative stress in renal tubules is initiated by reactive oxygen species (ROS) and intracellular Ca2+elevation [5].
Ranolazine (RAN) is an antianginal drug that has been studied for several purposes [6]. RAN prevents the increase in Na+ by blocking late Na+ channels and the accumulation of cellular Ca2+ through Na/Ca2+ exchange (NCX) and restores mitochondrial function, thereby exerting an antioxidant effect by preventing the formation of ROS [7, 8]. It has been shown that oxidative stress triggers the late Na+ channel, and the accumulation of Na+ and Ca2+ is the main mechanism in organ damage [9]. Thus, RAN can counteract the harmful effects of oxidative stress [10].
Currently, preventive strategies, such as monitoring kidney function before starting nephrotoxic drugs, close patient follow-up, and fluid administration, are recommended to prevent CIS-induced nephrotoxicity [11]. However, CIS nephrotoxicity remains a significant clinical problem that requires effective solutions. CIS and RAN have opposing effects mediated by common mechanisms, such as oxidant-antioxidant enzyme levels. Therefore, we aimed to evaluate the protective and therapeutic effects of RAN against CIS-induced nephrotoxicity in terms of oxidative stress, renal function markers, and histopathological parameters.