Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.

<h4>Introduction</h4>Acute kidney injury is a serious,sexually dimorphic perioperative complication, primarily attributed to hypoperfusion. We previously found that estradiol is renoprotective after cardiac arrest and cardiopulmonary resuscitation in ovariectomized female mice. Additiona...

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Autores principales: Michael P Hutchens, Yasuharu Kosaka, Wenri Zhang, Tetsuhiro Fujiyoshi, Stephanie Murphy, Nabil Alkayed, Sharon Anderson
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:c149097155e6460c97ef37ad6ffb8ff42021-11-18T08:15:49ZEstrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.1932-620310.1371/journal.pone.0099910https://doaj.org/article/c149097155e6460c97ef37ad6ffb8ff42014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24923556/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Acute kidney injury is a serious,sexually dimorphic perioperative complication, primarily attributed to hypoperfusion. We previously found that estradiol is renoprotective after cardiac arrest and cardiopulmonary resuscitation in ovariectomized female mice. Additionally, we found that neither estrogen receptor alpha nor beta mediated this effect. We hypothesized that the G protein estrogen receptor (GPR30) mediates the renoprotective effect of estrogen.<h4>Methods</h4>Ovariectomized female and gonadally intact male wild-type and GPR30 gene-deleted mice were treated with either vehicle or 17β-estradiol for 7 days, then subjected to cardiac arrest and cardiopulmonary resuscitation. Twenty four hours later, serum creatinine and urea nitrogen were measured, and histologic renal injury was evaluated by unbiased stereology.<h4>Results</h4>In both males and females, GPR30 gene deletion was associated with reduced serum creatinine regardless of treatment. Estrogen treatment of GPR30 gene-deleted males and females was associated with increased preprocedural weight. In ovariectomized female mice, estrogen treatment did not alter resuscitation, but was renoprotective regardless of GPR30 gene deletion. In males, estrogen reduced the time-to-resuscitate and epinephrine required. In wild-type male mice, serum creatinine was reduced, but neither serum urea nitrogen nor histologic outcomes were affected by estrogen treatment. In GPR30 gene-deleted males, estrogen did not alter renal outcomes. Similarly, renal injury was not affected by G1 therapy of ovariectomized female wild-type mice.<h4>Conclusion</h4>Treatment with 17β-estradiol is renoprotective after whole-body ischemia-reperfusion in ovariectomized female mice irrespective of GPR30 gene deletion. Treatment with the GPR30 agonist G1 did not alter renal outcome in females. We conclude GPR30 does not mediate the renoprotective effect of estrogen in ovariectomized female mice. In males, estrogen therapy was not renoprotective. Estrogen treatment of GPR30 gene-deleted mice was associated with increased preprocedural weight in both sexes. Of significance to further investigation, GPR30 gene deletion was associated with reduced serum creatinine, regardless of treatment.Michael P HutchensYasuharu KosakaWenri ZhangTetsuhiro FujiyoshiStephanie MurphyNabil AlkayedSharon AndersonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e99910 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Michael P Hutchens
Yasuharu Kosaka
Wenri Zhang
Tetsuhiro Fujiyoshi
Stephanie Murphy
Nabil Alkayed
Sharon Anderson
Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.
description <h4>Introduction</h4>Acute kidney injury is a serious,sexually dimorphic perioperative complication, primarily attributed to hypoperfusion. We previously found that estradiol is renoprotective after cardiac arrest and cardiopulmonary resuscitation in ovariectomized female mice. Additionally, we found that neither estrogen receptor alpha nor beta mediated this effect. We hypothesized that the G protein estrogen receptor (GPR30) mediates the renoprotective effect of estrogen.<h4>Methods</h4>Ovariectomized female and gonadally intact male wild-type and GPR30 gene-deleted mice were treated with either vehicle or 17β-estradiol for 7 days, then subjected to cardiac arrest and cardiopulmonary resuscitation. Twenty four hours later, serum creatinine and urea nitrogen were measured, and histologic renal injury was evaluated by unbiased stereology.<h4>Results</h4>In both males and females, GPR30 gene deletion was associated with reduced serum creatinine regardless of treatment. Estrogen treatment of GPR30 gene-deleted males and females was associated with increased preprocedural weight. In ovariectomized female mice, estrogen treatment did not alter resuscitation, but was renoprotective regardless of GPR30 gene deletion. In males, estrogen reduced the time-to-resuscitate and epinephrine required. In wild-type male mice, serum creatinine was reduced, but neither serum urea nitrogen nor histologic outcomes were affected by estrogen treatment. In GPR30 gene-deleted males, estrogen did not alter renal outcomes. Similarly, renal injury was not affected by G1 therapy of ovariectomized female wild-type mice.<h4>Conclusion</h4>Treatment with 17β-estradiol is renoprotective after whole-body ischemia-reperfusion in ovariectomized female mice irrespective of GPR30 gene deletion. Treatment with the GPR30 agonist G1 did not alter renal outcome in females. We conclude GPR30 does not mediate the renoprotective effect of estrogen in ovariectomized female mice. In males, estrogen therapy was not renoprotective. Estrogen treatment of GPR30 gene-deleted mice was associated with increased preprocedural weight in both sexes. Of significance to further investigation, GPR30 gene deletion was associated with reduced serum creatinine, regardless of treatment.
format article
author Michael P Hutchens
Yasuharu Kosaka
Wenri Zhang
Tetsuhiro Fujiyoshi
Stephanie Murphy
Nabil Alkayed
Sharon Anderson
author_facet Michael P Hutchens
Yasuharu Kosaka
Wenri Zhang
Tetsuhiro Fujiyoshi
Stephanie Murphy
Nabil Alkayed
Sharon Anderson
author_sort Michael P Hutchens
title Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.
title_short Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.
title_full Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.
title_fullStr Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.
title_full_unstemmed Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion.
title_sort estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to gpr30 gene deletion.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/c149097155e6460c97ef37ad6ffb8ff4
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AT yasuharukosaka estrogenmediatedrenoprotectionfollowingcardiacarrestandcardiopulmonaryresuscitationisrobusttogpr30genedeletion
AT wenrizhang estrogenmediatedrenoprotectionfollowingcardiacarrestandcardiopulmonaryresuscitationisrobusttogpr30genedeletion
AT tetsuhirofujiyoshi estrogenmediatedrenoprotectionfollowingcardiacarrestandcardiopulmonaryresuscitationisrobusttogpr30genedeletion
AT stephaniemurphy estrogenmediatedrenoprotectionfollowingcardiacarrestandcardiopulmonaryresuscitationisrobusttogpr30genedeletion
AT nabilalkayed estrogenmediatedrenoprotectionfollowingcardiacarrestandcardiopulmonaryresuscitationisrobusttogpr30genedeletion
AT sharonanderson estrogenmediatedrenoprotectionfollowingcardiacarrestandcardiopulmonaryresuscitationisrobusttogpr30genedeletion
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