Email updates

Keep up to date with the latest news and content from Critical Care and BioMed Central.

Open Access Research

Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose

Runkuan Yang12*, Xiaoping Zou3, Marja-Leena Koskinen4 and Jyrki Tenhunen2

Author Affiliations

1 Department of Critical Care Medicine, University of Pittsburgh Medical School, 3550 Terrace Street, Pittsburgh, PA 15261, USA

2 Department of Intensive Care Medicine, University of Tampere Medical School, 10 Bio katu, 33521 Tampere, Finland

3 Department of Gastroenterology, Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Street, 210008 Nanjing, China

4 Department of Pathology, University of Tampere Medical School, 10 Bio katu, 33521 Tampere, Finland

For all author emails, please log on.

Critical Care 2012, 16:R9  doi:10.1186/cc11149

Published: 16 January 2012

Abstract

Introduction

Inflammation may critically affect mechanisms of liver injury in acetaminophen (APAP) hepatotoxicity. Kupffer cells (KC) play important roles in inflammation, and KC depletion confers protection at early time points after APAP treatment but can lead to more severe injury at a later time point. It is possible that some inflammatory factors might contribute to liver damage at an early injurious phase but facilitate liver regeneration at a late time point. Therefore, we tested this hypothesis by using ethyl pyruvate (EP), an anti-inflammatory agent, to treat APAP overdose for 24-48 hours.

Methods

C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). Following 2 hours of APAP challenge, the mice were given 0.5 mL EP (40 mg/kg) or saline treatment every 8 hours for a total of 24 or 48 hours.

Results

Twenty-four hours after APAP challenge, compared to the saline-treated group, EP treatment significantly lowered serum transaminases (ALT/AST) and reduced liver injury seen in histopathology; however, at the 48-hour time point, compared to the saline therapy, EP therapy impaired hepatocyte regeneration and increased serum AST; this late detrimental effect was associated with reduced serum TNF-α concentration and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration.

Conclusions

Inflammation likely contributes to liver damage at an early injurious phase but improves hepatocyte regeneration at a late time point, and prolonged anti-inflammation therapy at a late phase is not beneficial.