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Lipopolysaccharide‐binding protein modulates acetaminophen‐induced liver injury in mice
Author(s) -
Su Grace L.,
Gong Ke Qin,
Fan Ming Hui,
Kelley William M.,
Hsieh Jason,
Sun Jian Min,
Hemmila Mark R.,
Arbabi Saman,
Remick Daniel G.,
Wang Stewart C.
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20533
Subject(s) - acetaminophen , hepatology , liver injury , lipopolysaccharide binding protein , medicine , lipopolysaccharide , necrosis , tumor necrosis factor alpha , toxicity , acetaminophen overdose , knockout mouse , pharmacology , inflammation , chemistry , acute phase protein , biochemistry , receptor , acetylcysteine , antioxidant
Acetaminophen toxicity is the most common cause of acute liver failure in the United States and Europe. Although much is known about the metabolism of acetaminophen, many questions remain regarding the pathogenesis of liver injury. In this study, we examined the role of lipopolysaccharide-binding protein (LBP), a protein important in mediating cellular response to lipopolysaccharides, by using LBP wild-type and knockout (KO) mice. We found that LBP KO mice were protected from acetaminophen-induced hepatotoxicity. At 350 mg/kg of acetaminophen, LBP KO mice had significantly less liver injury and necrosis than wild-type mice. Repletion studies in LBP KO mice using an LBP-adenoviral construct resulted in significantly more hepatic injury and necrosis after acetaminophen exposure compared with mice receiving the control adenoviral construct. In conclusion, LBP KO mice are protected from toxicity with a decrease in hepatic necrosis following acetaminophen challenge. This suggests a novel role for LBP in modulating acetaminophen-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/O270-9139/suppmat/index.html).