Inhibition of xanthine oxidoreductase protects against contrast-induced renal tubular injury by activating adenosine monophosphate-activated protein kinase.

Inhibition of xanthine oxidoreductase protects against contrast-induced renal tubular injury by activating adenosine monophosphate-activated protein kinase. Free Radic Biol Med. 2019 Sep 24;: Authors: Yang KJ, Kim JH, Chang YK, Park CW, Kim SY, Hong YA Abstract Reactive oxygen species (ROS) play a pivotal role in the development of contrast-induced nephropathy (CIN). The inhibition of xanthine oxidoreductase is known to reduce levels of ROS. We investigated whether febuxostat could attenuate oxidative stress via the activation of adenosine monophosphate-activated protein kinase (AMPK) against CIN. In a mouse model of CIN, renal impairment and tubular injury substantially increased, whereas febuxostat attenuated renal injury. Plasma and kidney xanthine oxidoreductase levels were decreased by febuxostat. Febuxostat administration was accompanied by the upregulation of AMPK phosphorylation and the inhibition of nicotinamide-adenine dinucleotide phosphate oxidase (Nox)1 and Nox2, followed by the inhibition of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 expressions and the suppression of transcription factor forkhead box O (FoxO)1 and FoxO3a phosphorylation. Cell survival was significantly reduced after iohexol administration and febuxostat ameliorated iohexol-induced cell death in proximal tubular (HK-2) cells. Furthermore, febuxostat enhanced AMPK phosphorylation and inhibited Nox1, Nox2, and HIF-1α expression in iohexo...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research