Emerging Role of Ferroptosis in Acute Kidney Injury

Zhaoxin Hu,Hao Zhang,Xueqin Wu,Shi-Kun Yang,Ke Cao,Dong He,Wei Zhang

doi:10.1155/2019/8010614

Abstract

Acute kidney injury (AKI) is a heterogeneous group of critical disease conditions with high incidence and mortality. Vasoconstriction, oxidative stress, apoptosis, and inflammation are generally thought to be the main pathogenic mechanisms of AKI. Ferroptosis is a type of iron-dependent nonapoptotic cell death characterized by membrane lipid peroxide accumulation and polyunsaturated fatty acid consumption, and it plays essential roles in many diseases, including cancers and neurologic diseases. Recent studies have revealed an emerging role of ferroptosis in the pathophysiological processes of AKI. Here, in the present review, we summarized the most recent discoveries on the role of ferroptosis in the pathogenesis of AKI as well as its therapeutic potential in AKI.

Highlights

Acute kidney injury (AKI), formerly known as acute renal failure (ARF), is a common and critical illness caused by multiple causes, including ischemia, nephrotoxic drugs, and urinary tract obstruction [1]
In 2012, Dixon et al proposed a new concept of cell death, namely, ferroptosis [7], which was subsequently demonstrated to be involved in diseases such as cancers and in neurological disorders including Huntington disease and periventricular leukomalacia [8, 9]
Ferroptosis, which represents a unique form of regulated cell death, has been reported to be involved in the development of multiple cancers and neurologic diseases

Summary

Introduction

Acute kidney injury (AKI), formerly known as acute renal failure (ARF), is a common and critical illness caused by multiple causes, including ischemia, nephrotoxic drugs, and urinary tract obstruction [1]. Ferroptosis is iron-dependent nonapoptotic cell death and is characterized by the accumulation of membrane lipid peroxidation products and the consumption of plasma membrane polyunsaturated fatty acids. The biological properties of ferroptosis are characterized by iron and ROS aggregation, which inhibit the activities of system xc- and GPX4 by reducing cystine uptake, depleting GSH, and releasing arachidonic acid and other molecules [13]. The application of ferroptosis inhibitors like ferrostatin-1 and liproxstatin-1 was a necessary method to observe and demonstrate the occurrence of ferroptosis

Key Regulators of Ferroptosis

Ferroptosis and AKI

Treatment of AKI by Targeting Ferroptosis

Findings

Conclusion