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

Am J Physiol Renal Physiol. 2021 Feb 22. doi: 10.1152/ajprenal.00016.2021. Online ahead of print.ABSTRACTRegulated 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.PMID:33615890 | DOI:10.11...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Source Type: research