Ethyl Pyruvate Reduces Mortality in an Endotoxin-induced Severe Acute Lung Injury Mouse Model

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2009 Oct 6

PMID 19799777

Citations 17

Authors

Guan-Hong Shang

Dian-Jie Lin

Wei Xiao

Chong-qi Jia

Yu Li

Ai-Hua Wang

Liang Dong

Affiliations

Soon will be listed here.

Abstract

Background: Ethyl pyruvate (EP) was recently identified as an experimental therapeutic agent in a wide variety of model systems for inflammation-mediated tissue and cellular injury.

Objective: To evaluate the effect of ethyl EP on improving the survival in mice with LPS-induced acute lung injury (ALI).

Methods: ALI was induced by administering lipopolysaccharide (LPS) intratracheally. The mice were treated intraperitoneally (i.p.) with 100, 50 and 10 mg/kg EP immediately before intratracheal instillation of LPS, and 100 mg/kg EP was administered 0, 12, 24 and 48 hours after induction of ALI. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL) -6 and IL-1 beta were measured in bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured by Western immunoblotting.

Results: Treatment with EP significantly inhibited the release of HMGB1, TNF-alpha, IL-6 and IL-1beta into bronchoalveolar lavage (BAL) fluids of ALI mice, and reduced the permeability index of the injured lung. High EP doses reduced the mortality from ALI and the permeability index (100 mg/kg and 50 mg/kg EP versus control; P < 0.0001). Early administration of high-dose EP significantly increased survival rate (0, 12 and 24 h versus control; P < 0.0001, P < 0.0001 and P = 0.01 respectively by log-rank test). There was no survival advantage when EP was initiated at 48 h.

Conclusion: Ethyl pyruvate improves survival and reduces the lung permeability index in mice with LPS-induced ALI.

Citing Articles

Ethyl pyruvate attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells: Role of GAS6/Axl signaling.

Chen Y, Chen J, Zhao L, Zhang X, Wu X, Wang X Heliyon. 2023; 9(12):e22787.

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Ethyl Pyruvate as a Potential Defense Intervention against Cytokine Storm in COVID-19?.

Tanwar O, Soni A, Prajapat P, Shivhare T, Pandey P, Samaiya P ACS Omega. 2021; 6(11):7754-7760.

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Ethyl pyruvate attenuates ventilation-induced diaphragm dysfunction through high-mobility group box-1 in a murine endotoxaemia model.

Liu Y, Chen N, Chang C, Lin S, Kao K, Hu H J Cell Mol Med. 2019; 23(8):5679-5691.

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Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases.

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HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma.

Pellegrini L, Xue J, Larson D, Pastorino S, Jube S, Forest K Oncotarget. 2017; 8(14):22649-22661.

PMID: 28186988 PMC: 5410252. DOI: 10.18632/oncotarget.15152.

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