Dexamethasone ameliorates renal ischemia-reperfusion injury

Sanjeev Kumar, David A. Allen, Julius E. Kieswich, Nimesh S A Patel, Steven Harwood, Emanuela Mazzon, Salvatore Cuzzocrea, Martin J. Raftery, Christoph Thiemermann, Muhammad M. Yaqoob

Research output: Contribution to journalArticlepeer-review


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, non-genomic mechanism.

Original languageEnglish
Pages (from-to)2412-2425
Number of pages14
JournalJournal of the American Society of Nephrology
Issue number11
Publication statusPublished - Nov 2009

ASJC Scopus subject areas

  • Nephrology


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