Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice

Grace L. Su, Ke Qin Gong, Ming Hui Fan, William Kelley, Jason Hsieh, Jian Min Sun, Mark R. Hemmila, Saman Arbabi, Daniel G. Remick, Stewart C. Wang

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalHepatology
Volume41
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

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Acetaminophen
Knockout Mice
Liver
Wounds and Injuries
Necrosis
Acute Liver Failure
lipopolysaccharide-binding protein
Lipopolysaccharides

ASJC Scopus subject areas

  • Hepatology

Cite this

Su, G. L., Gong, K. Q., Fan, M. H., Kelley, W., Hsieh, J., Sun, J. M., ... Wang, S. C. (2005). Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice. Hepatology, 41(1), 187-195. https://doi.org/10.1002/hep.20533

Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice. / Su, Grace L.; Gong, Ke Qin; Fan, Ming Hui; Kelley, William; Hsieh, Jason; Sun, Jian Min; Hemmila, Mark R.; Arbabi, Saman; Remick, Daniel G.; Wang, Stewart C.

In: Hepatology, Vol. 41, No. 1, 01.2005, p. 187-195.

Research output: Contribution to journalArticle

Su, GL, Gong, KQ, Fan, MH, Kelley, W, Hsieh, J, Sun, JM, Hemmila, MR, Arbabi, S, Remick, DG & Wang, SC 2005, 'Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice', Hepatology, vol. 41, no. 1, pp. 187-195. https://doi.org/10.1002/hep.20533
Su, Grace L. ; Gong, Ke Qin ; Fan, Ming Hui ; Kelley, William ; Hsieh, Jason ; Sun, Jian Min ; Hemmila, Mark R. ; Arbabi, Saman ; Remick, Daniel G. ; Wang, Stewart C. / Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice. In: Hepatology. 2005 ; Vol. 41, No. 1. pp. 187-195.
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