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

doi:10.3892/ijmm.2016.2665

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

Authors:
- Guofu Li
- Jia Jia
- Kaiqiang Ji
- Xiaoying Gong
- Rui Wang
- Xiaoli Zhang
- Haiyuan Wang
- Bin Zang
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Affiliations: Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: July 5, 2016 https://doi.org/10.3892/ijmm.2016.2665
Pages: 767-775
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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