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

Content Provider	Springer Nature : BioMed Central
Author	Yang, Runkuan Zou, Xiaoping Koskinen, Marja-Leena Tenhunen, Jyrki
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.
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc11149.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/cc11149
Journal	Critical Care
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2012-01-16
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine APAP Acute Liver Injury Infiltrate Inflammatory Cell Ethyl Pyruvate APAP Overdose
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

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