Regulated cell death in cisplatin-induced AKI: relevance of myo-inositol metabolism

Abstract

Regulated cell death (RCD), distinct from accidental cell death, refers to a process ofwell-controlled programmed cell death with well-defined pathological mechanisms. In thepast few decades, various terms for RCDs were coined, and some of them have beenimplicated in the pathogenesis of various types of acute kidney injury (AKI). Cisplatin iswidely used as a chemotherapeutic drug for a broad spectrum of cancers, but its usagewas hampered because of being highly nephrotoxic. Cisplatin-induced AKI is commonlyseen clinically, and it also serves as a well-established prototypic model for laboratoryinvestigations relevant to acute nephropathy affecting especially the tubular compartment.Literature reports over a period of three decades indicate that there are multiple types ofRCDs, including apoptosis, necroptosis, pyroptosis, ferroptosis and mitochondrial permeability transition (MPT)-mediated necrosis, and some of them are pertinent to the pathogenesis of cisplatin-induced AKI. Interestingly, myo-inositol metabolism, a vital biological process that is largely restricted to the kidney, seems to be relevant to thepathogenesis of certain forms of RCDs. A comprehensive understanding of the RCDs in cisplatin-induced AKI and their relevance to myo-inositol homeostasis may yield novel therapeutic targets for the amelioration of cisplatin-related nephropathy.

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

“…Recommended as a first-line chemotherapeutic, cisplatin is applied in the treatment of various types of malignancies, including lymphoma, germ cell carcinomas, and neoplasms of the prostate, bladder, and lung [ 1 ]. Cisplatin freely passes through glomerular filter and is largely reabsorbed by proximal tubules (especially S3 segment tubules), and such localized accumulation may result in nephrotoxicity [ 43 ]. As early as 30 years ago, researchers proposed that cisplatin-induced free iron overload leads to lipid peroxidation in kidneys, but the link between ferroptosis and Cis-AKI has only recently been recognized.…”

Leonurine alleviates ferroptosis in cisplatin‐induced acute kidney injury by activating the Nrf2 signalling pathway

“…As the exact molecular mechanisms by which cisplatin induces acute kidney injury are not fully understood, strategies for the prevention and treatment of cisplatin induced acute kidney injury are limited. Tubular cell injury and death play vital roles in the initiation and progression of acute kidney injury (Deng et al, 2021; Linkermann et al, 2014). Previous studies focused on the induction of renal tubular cell apoptosis and necrosis by cisplatin, but specific inhibitors of both apoptosis and necrosis failed to completely prevent or stop cisplatin‐acute kidney injury (Herzog et al, 2012; Tristão et al, 2012).…”

Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway

“…Numerous studies focusing on the tubular compartment have been carried out over several decades, utilizing various animal models to investigate the pathogenesis of human AKI ( 4 ). Among various models, ischemia- and cisplatin-induced tubular injury are the 2 major animal model systems that were utilized to delineate a number of diverse pathogenetic mechanisms relative to AKI, and this has been the subject of recent reviews ( 5 – 7 ).…”