Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury

Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min is...

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Main Authors:	Lempiäinen, Juha, Finckenberg, Piet, Mervaala, Elina E, Storvik, Markus, Kaivola, Juha, Lindstedt, Ken, Levijoki, Jouko, Mervaala, Eero M
Format:	Online
Language:	English
Published:	Blackwell Publishing Ltd 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186414/

id	pubmed-4186414
recordtype	oai_dc
spelling	pubmed-41864142014-12-03 Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury Lempiäinen, Juha Finckenberg, Piet Mervaala, Elina E Storvik, Markus Kaivola, Juha Lindstedt, Ken Levijoki, Jouko Mervaala, Eero M Original Articles Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning. Blackwell Publishing Ltd 2014-06 2014-04-22 /pmc/articles/PMC4186414/ /pubmed/25505591 http://dx.doi.org/10.1002/prp2.45 Text en © 2014 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lempiäinen, Juha Finckenberg, Piet Mervaala, Elina E Storvik, Markus Kaivola, Juha Lindstedt, Ken Levijoki, Jouko Mervaala, Eero M
spellingShingle	Lempiäinen, Juha Finckenberg, Piet Mervaala, Elina E Storvik, Markus Kaivola, Juha Lindstedt, Ken Levijoki, Jouko Mervaala, Eero M Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
author_facet	Lempiäinen, Juha Finckenberg, Piet Mervaala, Elina E Storvik, Markus Kaivola, Juha Lindstedt, Ken Levijoki, Jouko Mervaala, Eero M
author_sort	Lempiäinen, Juha
title	Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
title_short	Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
title_full	Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
title_fullStr	Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
title_full_unstemmed	Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
title_sort	dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
description	Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning.
publisher	Blackwell Publishing Ltd
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186414/
_version_	1613141163954405376

Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury

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