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

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dc.contributor.author Yang, Runkuan -
dc.contributor.author Zou, Xiaoping -
dc.contributor.author Koskinen, Marja-Leena -
dc.contributor.author Tenhunen, Jyrki -
dc.date.accessioned 2012-06-17T20:15:29Z
dc.date.available 2012-06-15 06:33:44 -
dc.date.available 2012-06-17T20:15:29Z
dc.date.issued 2012 -
dc.identifier.issn 1466-609X -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66093
dc.description BioMed Central open access -
dc.description.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. -
dc.language.iso en -
dc.title Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-945 -
dc.identifier.doi doi:10.1186/cc11149 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Kirurgia, anestesiologia, tehohoito, radiologia | en=Surgery, Anesthesiology, Intensive Care| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title Critical Care -
dc.journal.volume 16 -
dc.journal.number 1 -
dc.journal.volumepagerange 1-9 -
dc.journal.url http://ccforum.com/content/16/1/R9
dc.oldstats 38 -

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