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 journalArticle

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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, non-genomic mechanism.

Original languageEnglish
Pages (from-to)2412-2425
Number of pages14
JournalJournal of the American Society of Nephrology
Volume20
Issue number11
DOIs
Publication statusPublished - Nov 2009

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Reperfusion Injury
Dexamethasone
Kidney
Neutrophils
Ischemia
Apoptosis
Caspase 9
Mitogen-Activated Protein Kinase Kinases
Glucocorticoid Receptors
Intercellular Adhesion Molecule-1
Starvation
Acute Kidney Injury
Caspase 3
Glucocorticoids
Reperfusion
Necrosis
Down-Regulation
Phosphorylation
Wounds and Injuries
Serum

ASJC Scopus subject areas

  • Nephrology

Cite this

Kumar, S., Allen, D. A., Kieswich, J. E., Patel, N. S. A., Harwood, S., Mazzon, E., ... Yaqoob, M. M. (2009). Dexamethasone ameliorates renal ischemia-reperfusion injury. Journal of the American Society of Nephrology, 20(11), 2412-2425. https://doi.org/10.1681/ASN.2008080868

Dexamethasone ameliorates renal ischemia-reperfusion injury. / Kumar, Sanjeev; Allen, David A.; Kieswich, Julius E.; Patel, Nimesh S A; Harwood, Steven; Mazzon, Emanuela; Cuzzocrea, Salvatore; Raftery, Martin J.; Thiemermann, Christoph; Yaqoob, Muhammad M.

In: Journal of the American Society of Nephrology, Vol. 20, No. 11, 11.2009, p. 2412-2425.

Research output: Contribution to journalArticle

Kumar, S, Allen, DA, Kieswich, JE, Patel, NSA, Harwood, S, Mazzon, E, Cuzzocrea, S, Raftery, MJ, Thiemermann, C & Yaqoob, MM 2009, 'Dexamethasone ameliorates renal ischemia-reperfusion injury', Journal of the American Society of Nephrology, vol. 20, no. 11, pp. 2412-2425. https://doi.org/10.1681/ASN.2008080868
Kumar, Sanjeev ; Allen, David A. ; Kieswich, Julius E. ; Patel, Nimesh S A ; Harwood, Steven ; Mazzon, Emanuela ; Cuzzocrea, Salvatore ; Raftery, Martin J. ; Thiemermann, Christoph ; Yaqoob, Muhammad M. / Dexamethasone ameliorates renal ischemia-reperfusion injury. In: Journal of the American Society of Nephrology. 2009 ; Vol. 20, No. 11. pp. 2412-2425.
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