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.