Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 28, 2012; 18(40): 5709-5718
Published online Oct 28, 2012. doi: 10.3748/wjg.v18.i40.5709
Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats
Lu-Wen Wang, Li-Kun Wang, Hui Chen, Cheng Fan, Xun Li, Can-Ming He, Zuo-Jiong Gong
Lu-Wen Wang, Li-Kun Wang, Cheng Fan, Xun Li, Can-Ming He, Zuo-Jiong Gong, Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Hui Chen, Institute of Infectious Diseases, Hubei Center for Disease Control and Prevention, Wuhan 430079, Hubei Province, China
Author contributions: Gong ZJ conceived and designed the research; Wang LW, Wang LK, Chen H, Fan C, Li X and He CM performed the research; Wang LW, Wang LK and Li X analyzed the data; Wang LW drafted the manuscript; Gong ZJ revised the manuscript; all authors have read and approved the final version to be published.
Supported by The National Natural Science Foundation of China, No. 81071342
Correspondence to: Zuo-Jiong Gong, MD, PhD, Professor, Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China. zjgong@163.com
Telephone: +86-27-88041911 Fax: +86-27-88042922
Received: April 1, 2012
Revised: May 21, 2012
Accepted: July 28, 2012
Published online: October 28, 2012
Abstract

AIM: To investigate the protective effects of ethyl pyruvate (EP) on acute-on-chronic liver failure (ACLF) in rats.

METHODS: An ACLF model was established in rats, and animals were randomly divided into normal, model and EP treatment groups. The rats in EP treatment group received EP (40 mg/kg) at 3 h, 6 h, 12 h and 24 h after induction of ACLF. Serum endotoxin, high mobility group box-1 (HMGB1), alanine transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-α (IFN-γ), interleukin (IL)-10 and IL-18 levels, changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF. The effects of EP on the survival of ACLF rats were also observed.

RESULTS: Serum levels of endotoxin (0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL, P < 0.001), HMGB1 (35.42 ± 10.86 μg/L vs 2.14 ± 0.27 μg/L, P < 0.001), ALT (8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L, P < 0.001), TNF-α (190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L, P < 0.001), IFN-γ (715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L, P < 0.001), IL-10 (6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L, P < 0.001) and IL-18 (85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L, P < 0.001) were significantly increased, and liver tissues presented severe pathological injury in the model group compared with the normal group. However, EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin (0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL, P < 0.001) and inflammatory cytokines (11.13 ± 2.58 μg/L vs 35.42 ± 10.86 μg/L for HMGB1, 3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT, 128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-α, 438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-γ, 3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10, and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18, respectively, P < 0.001), and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF. EP treatment at the four time points prolonged the median survival time of ACLF rats (60 h) to 162 h, 120 h, 102 h and 78 h, respectively (χ2 = 41.17, P < 0.0001).

CONCLUSION: EP administration can protect against ACLF in rats, and is a potential and novel therapeutic agent for severe liver injury.

Keywords: Acute-on-chronic liver failure, Ethyl pyruvate, High mobility group box-1, Inflammatory cytokines, Histopathology, Survival time