Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury

Abstract

Ferroptosis is a recently recognized form of nonapoptotic cell death that is triggered by reactive oxidative species (ROS) due to iron overload, lipid peroxidation accumulation, or the inhibition of phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Recent studies have reported that ferroptosis plays a vital role in the pathophysiological process of multiple systems such as the nervous, renal, and pulmonary systems. In particular, the kidney has higher rates of O2 consumption in its mitochondria than other organs; therefore, it is susceptible to imbalances between ROS and antioxidants. In ischemia/reperfusion (I/R) injury, which is damage caused by the restoring blood flow to ischemic tissues, the release of ROS and reactive nitrogen species is accelerated and contributes to subsequent inflammation and cell death, such as ferroptosis, as well as apoptosis and necrosis being induced. At the same time, I/R injury is one of the major causes of acute kidney injury (AKI), causing significant morbidity and mortality. This review highlights the current knowledge on the involvement of ferroptosis in AKI via oxidative stress.

Noncoding RNAs and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate

“…Another type of ncRNA, miRNAs, contributes to inhibiting tumor T A B L E 1 The comparison of apoptosis, ferroptosis, and necroptosis processes in terms of biochemical properties, main proteins, cell membrane, cell morphology, and nucleus (Hosohata et al, 2022). ways in colorectal cancer (Huang et al, 2022).…”

Prospects for Anti-Tumor Mechanism and Potential Clinical Application Based on Glutathione Peroxidase 4 Mediated Ferroptosis

“…In The Cancer Genome Project (TCGA) database, several researchers have reported that the expression of GPX4 is higher in various tumors than in normal tissues, including kidney chromophobe (KICH) [ 89 ], prostate adenocarcinoma (PRAD) [ 90 ], thyroid carcinoma (THCA) [ 91 ], colon adenocarcinoma (COAD) [ 92 ], kidney renal clear cell carcinoma (KIRC), cervical and endocervical cancer (CESC), lung adenocarcinoma (LUAD) [ 93 ], and rectum adenocarcinoma (READ). The expression of GPX4 is generally higher in patients with multiple cancers than in normal tissues.…”

Site 1 protease aggravates acute kidney injury by promoting tubular epithelial cell ferroptosis through SIRT3‐SOD2‐mtROS signaling

“…In ischemic kidney, lipid metabolism is dysregulated which is revealed by significantly accumulated lipid droplet in renal tubules and markedly elevated fatty acyls, triglycerides, and sphingolipids [5,29]. Characterized by accumulation of lipid hydroperoxides, ferroptosis is vital in the pathophysiological process of I/R induced AKI [15,30,31]. Hence, above evidence indicates the potential involvement S1P in renal ischemic injury.…”