The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats

Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclea...

Full description

Bibliographic Details
Main Authors:	Li, Guofu, Jia, Jia, Ji, Kaiqiang, Gong, Xiaoying, Wang, Rui, Zhang, Xiaoli, Wang, Haiyuan, Zang, Bin
Format:	Online
Language:	English
Published:	D.A. Spandidos 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990314/

id	pubmed-4990314
recordtype	oai_dc
spelling	pubmed-49903142016-08-26 The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats Li, Guofu Jia, Jia Ji, Kaiqiang Gong, Xiaoying Wang, Rui Zhang, Xiaoli Wang, Haiyuan Zang, Bin Articles Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury. D.A. Spandidos 2016-09 2016-07-05 /pmc/articles/PMC4990314/ /pubmed/27430552 http://dx.doi.org/10.3892/ijmm.2016.2665 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , 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	Li, Guofu Jia, Jia Ji, Kaiqiang Gong, Xiaoying Wang, Rui Zhang, Xiaoli Wang, Haiyuan Zang, Bin
spellingShingle	Li, Guofu Jia, Jia Ji, Kaiqiang Gong, Xiaoying Wang, Rui Zhang, Xiaoli Wang, Haiyuan Zang, Bin The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
author_facet	Li, Guofu Jia, Jia Ji, Kaiqiang Gong, Xiaoying Wang, Rui Zhang, Xiaoli Wang, Haiyuan Zang, Bin
author_sort	Li, Guofu
title	The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
title_short	The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
title_full	The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
title_fullStr	The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
title_full_unstemmed	The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
title_sort	neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats
description	Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury.
publisher	D.A. Spandidos
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990314/
_version_	1613630148121198592

The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats

Similar Items