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Acute hydroxyurea treatment reduces tubular damage following bilateral ischemia-reperfusion injury in a mouse model of sickle cell disease.

Abstract：

:Ischemic injury is a primary contributor to the initiation of renal tubular epithelial cell damage in sickle cell disease (SCD). In this study, we investigated the effects of bilateral ischemia-reperfusion injury, which is a common type of acute kidney injury (AKI), in male and female genetic mouse model of SCD. Bilateral occlusion of both renal hila for 21 min led to a significantly higher detection of established serum markers of AKI (creatinine, KIM-1 and NGAL) compared to sham-operated male SCD mice. Severe damage to the outer medullary tubules was determined in the ischemia-reperfision injury (IRI)-treated SCD male mice. In female SCD mice with a longer ischemic time (23 min), the serum markers of AKI were not as highly elevated compared to their male counterparts, and the extent of outer medullary tubular injury was less severe. To assess the potential benefit in the use of hydroxyurea (50 mg/kg IP) following bilateral renal IRI, we observed that the serum markers of AKI and the outer medullary tubular damage were markedly improved compared to male SCD mice that were not treated with hydroxyurea. In this study, we confirmed that male SCD mice were more susceptible to increased tubular damage and a loss in renal function compared to female SCD mice, and that hydroxyurea may partially prevent the extent of tubular injury following severe ischemia-reperfusion injury in SCD.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Park F,Soni H,Pressly JD,Adebiyi A

doi

10.1016/j.bbrc.2019.05.116

subject

Has Abstract

pub_date

2019-07-12 00:00:00

pages

72-76

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)31002-2

journal_volume

515

pub_type

杂志文章

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