title: Modulation of d-galactosamine/lipopolysacharride-induced fulminant hepatic failure by nilotinib.
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.
authors.affiliation: 1 Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia.|2 Faculty of Pharmacy, Department of Pharmacology and Toxicology, Mansoura University, Mansoura, Egypt.
authors.forename: D S
authors.initials: DS
authors.lastname: El-Agamy
authors.affiliation: 3 Faculty of Medicine, Department of Pathology, Mansoura University, Mansoura, Egypt.
authors.forename: A M
authors.initials: AM
authors.lastname: Shebl
authors.affiliation: 2 Faculty of Pharmacy, Department of Pharmacology and Toxicology, Mansoura University, Mansoura, Egypt.
authors.forename: A A
authors.initials: AA
authors.lastname: Shaaban
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D005688:Galactosamine; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011743:Pyrimidines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C498826:nilotinib
keywords: Fulminant hepatic failure; d-galactosamine; lipopolysaccharide; nilotinib