Modulation of d-galactosamine/lipopolysacharride–induced fulminant hepatic failure by nilotinib

D. S. El-Agamy, A. M. Shebl, A. A. Shaaban*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

This investigation was undertaken to test the effect of nilotinib against d-galactosamine (GalN) and lipopolysaccharide (LPS)–induced fulminant hepatic failure (FHF). Male Swiss albino mice were orally treated with nilotinib for 3 days prior to GalN/LPS challenge. The results revealed that administration of GalN/LPS caused elevation in the mortality rate. GalN/LPS-induced severe hepatic injury was manifested by increased serum transaminases and alkaline phosphatase (ALP) levels as well as histopathological hepatic necrosis and inflammation. In addition, GalN/LPS increased the hepatic oxidative stress as indicated by increased malondialdehyde level, decreased glutathione content, and superoxide dismutase (SOD) activity. Furthermore, GalN/LPS increased nuclear factor kappa-B activation and the levels of tumor necrosis factor-alpha and interleukin-1β. These biochemical and histopathological changes were markedly ameliorated by nilotinib pretreatment. On the other hand, the level of toll-like receptor-4 was increased upon GalN/LPS challenge, which was not alleviated by nilotinib pretreatment. These data demonstrate that nilotinib has hepatoprotective activity against GalN/LPS-mediated FHF in mice via anti-oxidative and anti-inflammatory effects.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalHuman and Experimental Toxicology
Volume37
Issue number1
DOIs
Publication statusPublished - Jan 1 2018
Externally publishedYes

Keywords

  • Fulminant hepatic failure
  • d-galactosamine
  • lipopolysaccharide
  • nilotinib

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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