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Exp Ther Med. 2014 Jul;8(1):95-99. Epub 2014 Apr 14.

NF-κB inhibition alleviates carbon tetrachloride-induced liver fibrosis via suppression of activated hepatic stellate cells.

Author information

  • 1Department of General Surgery Ward 1, Xinxiang Central Hospital, Xinxiang, Henan 453000, P.R. China.
  • 2Department of Infectious Diseases, Third Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan 453000, P.R. China.

Abstract

An effective treatment for hepatic fibrosis is not available clinically. Nuclear factor (NF)-κB plays a central role in inflammation and fibrosis. The aim of the present study was to investigate the effect of an NF-κB inhibitor, BAY-11-7082 (BAY), on mouse liver fibrosis. The effects of BAY on hepatic stellate cell (HSC) activation were measured in the lipopolysaccharide-activated rat HSC-T6 cell line. In addition, the therapeutic effect of BAY was studied in vivo using a model of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice. BAY effectively decreased the cell viability of activated HSC-T6 cells and suppressed HSC-T6 activation by downregulating the expression of collagen I and α-smooth muscle actin. BAY significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) in activated HSC-T6 cells. In addition, administration of BAY attenuated mouse liver fibrosis induced by CCl4, as shown by histology and the expression of profibrogenic markers. BAY also significantly decreased the levels of serum alanine aminotransferase in this model of hepatic fibrosis. Therefore, the results of the present study demonstrate that BAY attenuates liver fibrosis by blocking PI3K and Akt phosphorylation in activated HSCs. Thus, BAY demonstrates therapeutic potential as a treatment for hepatic fibrosis.

KEYWORDS:

BAY-11-7082; carbon tetrachloride; liver fibrosis; nuclear factor-κB

PMID:
24944604
[PubMed]
PMCID:
PMC4061207
Free PMC Article

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