Keywords
Radiation; Oxidative Reaction; Lipid Peroxidation; Radiation Nephropathy; Ferroptosis
Abstract
Radiation nephropathy is the damage to the renal parenchyma and blood vessels caused by ionizing radiation, and its mechanism of injury involves oxidative stress, DNA damage, cellular senescence, and other processes, among which oxidative stress plays an obvious role. In the case of excessive accumulation of oxidative stress products, it can lead to lipid peroxidation and iron distribution abnormalities caused by ferroptosis; the latter is involved in a variety of pathophysiological processes, while currently there is no role in radiation nephropathy. The present study sought to investigate the role of ferroptosis in radiation nephropathy, and the mechanism of FG-4592 in relieviating radiation nephropathy, C57BL/6 mice and TCMK-1 cell are separately irradiated with 12GY, 10GY X-ray to construct radiation nephropathy models in vivo and in vitro. Compared with the control group, X-rays promoted the occurrence of lipid peroxidation and ferroptosis, and oxidative stress and lipid peroxidation products were increased and antioxidant products were decreased in the X-rays-induced radionephropathy model; intervention in ferroptosis could alleviate radiation nephropathy, and FG-4592 could regulate lipid metabolism and oxidative reactions to ameliorate feroptosis and attenuate kidney injury through the modulation of HIF activity. In conclusion, in this study, transcriptome analysis was utilized to screen out the pathways involved in the regulation of radiation nephropathy, which provided the basis for the subsequent study of drug intervention in radioactive kidney injury. And FG-4592 had a certain anti-radiation effect in this experiment, which had a protective effect in radiation nephropathy. This study provides new ideas for the development of novel low toxicity, effective radiation-resistant agents.