Cargando…

Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation

ATP‐sensitive potassium channels (KATPs) have protective effects in ischemia–reperfusion‐induced injuries and can be activated by levosimendan. This study investigated the effects of levosimendan on renal injury, inflammation, apoptosis, and survival in a rat model of acute kidney injury (AKI) follo...

Descripción completa

Detalles Bibliográficos
Autores principales: Tian, Lei, Wang, Shiwei, Zhao, Li, Lu, Xiaoye, Zhu, Changqing, Gong, Hao, Yang, Weiqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329773/
https://www.ncbi.nlm.nih.gov/pubmed/34115930
http://dx.doi.org/10.1002/2211-5463.13227
_version_ 1783732574624940032
author Tian, Lei
Wang, Shiwei
Zhao, Li
Lu, Xiaoye
Zhu, Changqing
Gong, Hao
Yang, Weiqiang
author_facet Tian, Lei
Wang, Shiwei
Zhao, Li
Lu, Xiaoye
Zhu, Changqing
Gong, Hao
Yang, Weiqiang
author_sort Tian, Lei
collection PubMed
description ATP‐sensitive potassium channels (KATPs) have protective effects in ischemia–reperfusion‐induced injuries and can be activated by levosimendan. This study investigated the effects of levosimendan on renal injury, inflammation, apoptosis, and survival in a rat model of acute kidney injury (AKI) following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Rats underwent a 5‐min asphyxia‐based CA and resuscitation. The rats were treated with levosimendan after successful resuscitation. Renal functions, histological changes, inflammatory responses, and apoptosis were examined. NRK‐52E cells treated by hypoxia/reoxygenation (H/R) were used to establish an in vitro CA‐CPR model. Rats in the CA‐induced AKI group had a low survival rate and increased levels of creatinine, blood urea nitrogen, and proinflammatory cytokines, as well as increased tubular injury. These results were significantly reversed after treatment with levosimendan. Levosimendan downregulated the expression of the apoptosis‐related proteins Bax, cleaved caspase‐3, and cleaved caspase‐9, as well as upregulated Bcl‐2 and p‐ERK expression in vivo and in vitro. Thus, our data suggest that levosimendan reduces mortality and AKI following CA and CPR via suppression of inflammation and apoptosis, and activation of ERK signaling.
format Online
Article
Text
id pubmed-8329773
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-83297732021-08-09 Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation Tian, Lei Wang, Shiwei Zhao, Li Lu, Xiaoye Zhu, Changqing Gong, Hao Yang, Weiqiang FEBS Open Bio Research Articles ATP‐sensitive potassium channels (KATPs) have protective effects in ischemia–reperfusion‐induced injuries and can be activated by levosimendan. This study investigated the effects of levosimendan on renal injury, inflammation, apoptosis, and survival in a rat model of acute kidney injury (AKI) following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Rats underwent a 5‐min asphyxia‐based CA and resuscitation. The rats were treated with levosimendan after successful resuscitation. Renal functions, histological changes, inflammatory responses, and apoptosis were examined. NRK‐52E cells treated by hypoxia/reoxygenation (H/R) were used to establish an in vitro CA‐CPR model. Rats in the CA‐induced AKI group had a low survival rate and increased levels of creatinine, blood urea nitrogen, and proinflammatory cytokines, as well as increased tubular injury. These results were significantly reversed after treatment with levosimendan. Levosimendan downregulated the expression of the apoptosis‐related proteins Bax, cleaved caspase‐3, and cleaved caspase‐9, as well as upregulated Bcl‐2 and p‐ERK expression in vivo and in vitro. Thus, our data suggest that levosimendan reduces mortality and AKI following CA and CPR via suppression of inflammation and apoptosis, and activation of ERK signaling. John Wiley and Sons Inc. 2021-07-12 /pmc/articles/PMC8329773/ /pubmed/34115930 http://dx.doi.org/10.1002/2211-5463.13227 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Tian, Lei
Wang, Shiwei
Zhao, Li
Lu, Xiaoye
Zhu, Changqing
Gong, Hao
Yang, Weiqiang
Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation
title Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation
title_full Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation
title_fullStr Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation
title_full_unstemmed Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation
title_short Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation
title_sort renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and erk activation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329773/
https://www.ncbi.nlm.nih.gov/pubmed/34115930
http://dx.doi.org/10.1002/2211-5463.13227
work_keys_str_mv AT tianlei renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation
AT wangshiwei renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation
AT zhaoli renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation
AT luxiaoye renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation
AT zhuchangqing renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation
AT gonghao renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation
AT yangweiqiang renoprotectiveeffectsoflevosimendanonacutekidneyinjuryfollowingcardiacarrestviaantiinflammationantiapoptosisanderkactivation