氧化应激
氮氧化物4
活性氧
DNA损伤
脂质过氧化
化学
横纹肌溶解症
背景(考古学)
脂质氧化
急性肾损伤
生物化学
抗氧化剂
生物
内科学
医学
NADPH氧化酶
DNA
古生物学
作者
Song Zhao,Xueqiao Wang,Xiaoqing Zheng,Xin Liang,Zhigang Wang,Juanlian Zhang,Xudong Zhao,Songlin Zhuang,Qiuhui Pan,Fenyong Sun,Wenjun Shang,Jonathan Barasch,Andong Qiu
标识
DOI:10.1016/j.freeradbiomed.2021.07.025
摘要
Iron deficiency is the most common micronutrient deficiency worldwide. While iron deficiency is known to suppress embryonic organogenesis, its effect on the adult organ in the context of clinically relevant damage has not been considered. Here we report that iron deficiency is a risk factor for nephrotoxic intrinsic acute kidney injury of the nephron (iAKI). Iron deficiency exacerbated cisplatin-induced iAKI by markedly increasing non-heme catalytic iron and Nox4 protein which together catalyze production of hydroxyl radicals followed by protein and DNA oxidation, apoptosis and ferroptosis. Crosstalk between non-heme catalytic iron/Nox4 and downstream oxidative damage generated a mutual amplification cycle that facilitated rapid progression of cisplatin-induced iAKI. Iron deficiency also exacerbated a second model of iAKI, rhabdomyolysis, via increasing catalytic heme-iron. Heme-iron induced lipid peroxidation and DNA oxidation by interacting with Nox4-independent mechanisms, promoting p53/p21 activity and cellular senescence. Our data suggests that correcting iron deficiency and/or targeting specific catalytic iron species are strategies to mitigate iAKI in a wide range of patients with diverse forms of kidney injury.
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