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PMID: 19797168 Published · ppublish English Journal Article

Dexamethasone ameliorates renal ischemia-reperfusion injury.

Journal of the American Society of Nephrology : JASN ·Vol. 20 ·No. 11 ·2009-11-00 ·Pages 2412-25

Kumar S, Allen DA, Kieswich JE, Patel NS, Harwood S, Mazzon E, Cuzzocrea S, Raftery MJ, Thiemermann C, Yaqoob MM

Abstract

In the setting of renal ischemia-reperfusion injury (IRI), the effect and mechanism of action of glucocorticoids are not well understood. In rat renal IRI, a single dose of dexamethasone administered before ischemia, or at the onset of reperfusion, ameliorated biochemical and histologic acute kidney injury after 24 h. Dexamethasone upregulated Bcl-xL, downregulated ischemia-induced Bax, inhibited caspase-9 and caspase-3 activation, and reduced apoptosis and necrosis of proximal tubular cells. In addition, dexamethasone decreased the number of infiltrating neutrophils and ICAM-1. We observed the protective effect of dexamethasone in neutrophil-depleted mice, suggesting a neutrophil-independent mechanism. In vitro, dexamethasone protected human kidney proximal tubular (HK-2) cells during serum starvation and IRI-induced apoptosis, but inhibition of MEK 1/2 abolished its anti-apoptotic effects in these conditions. Dexamethasone stimulated rapid and transient phosphorylation of ERK 1/2, which required the presence of the glucocorticoid receptor and was independent of transcriptional activity. In summary, in the setting of renal ischemia-reperfusion injury, dexamethasone directly protects against kidney injury by a receptor-dependent, nongenomic mechanism.

MeSH Terms
Animals Apoptosis/drug effects,physiology Dexamethasone/therapeutic use Glucocorticoids/therapeutic use Kidney/blood supply Male Mice Mice, Inbred C57BL Neutrophils/drug effects,physiology Rats Rats, Wistar Reperfusion Injury/drug therapy
Chemicals
Glucocorticoids Dexamethasone
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kumar Sanjeev
Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, St. Bartholomew's, University of London, London EC1M 6BQ, United Kingdom. [email protected]
Allen David A
Kieswich Julius E
Patel Nimesh S A
Harwood Steven
Mazzon Emanuela
Cuzzocrea Salvatore
Raftery Martin J
Thiemermann Christoph
Yaqoob Muhammad M
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Article Info
Journal
Journal of the American Society of Nephrology : JASN
Abbr.
J Am Soc Nephrol
ISSN
1533-3450
DOI
10.1681/ASN.2008080868
Email
[email protected]
Published
2009-11-00
Epub
2009-00-24
Pages
2412-25
Language
English
Region
United States
NLM ID
9013836
PMCID
PMC2799171
Subset
IM
External Links
PubMed source DOI: 10.1681/ASN.2008080868 PMC Full Text View journal details
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