Iron deficiency exacerbates cisplatin- or rhabdomyolysis-induced acute kidney injury through promoting iron-catalyzed oxidative damage.

ABSTRACT: 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 e

SUBMITTER: Zhao S 

PROVIDER: S-EPMC9482792 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature