Hereditary hemochromatosis disrupts uric acid homeostasis and causes hyperuricemia via altered expression/activity of xanthine oxidase and ABCG2.

ABSTRACT: Hereditary hemochromatosis (HH) is mostly caused by mutations in the iron-regulatory gene HFE. The disease is associated with iron overload, resulting in liver cirrhosis/cancer, cardiomegaly, kidney dysfunction, diabetes, and arthritis. Fe2+-induced oxidative damage is suspected in the etiology of these symptoms. Here we examined, using Hfe-/- mice, whether disruption of uric acid (UA) homeostasis plays any role in HH-associated arthritis. We detected elevated levels of UA in serum and intestine in Hfe-/- mice compared with controls. Though the expression of xanthine oxidase, which generates UA, was not different in liver and intestine between wild type and Hfe-/- mice, the enzymatic activity was higher in Hfe-/- mice. We then examined various transporters involved in UA absorption/excreti

SUBMITTER: Ristic B 

PROVIDER: S-EPMC7200644 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature