Toxicogenomics Study on ${\alpha}-Naphthylisothiocyanate\;(ANIT)$ Induced Hepatotoxictiy in Mice

  • Hwang, Ji-Yoon (Toxicogenomics team, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Lim, Jung-Sun (Toxicogenomics team, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Jeong, Sun-Young (Toxicogenomics team, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Park, Han-Jin (Toxicogenomics team, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Cho, Jae-Woo (Toxicogenomics team, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Yoon, Seok-Joo (Toxicogenomics team, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology)
  • Published : 2006.03.31

Abstract

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

Keywords

References

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