Single injection of naked plasmid encoding α-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice

Cheng Haung Wang, Bruno Jawan, Tsung Hsing Lee, Kuo Sheng Hung, Wen Ying Chou, Cheng Nann Lu, Jong Kang Liu, Yann Jang Chen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Oxidative stress has been implicated in the propagation of acute liver injury. The aim of our study was to investigate whether gene transfer of α-melanocyte-stimulating hormone (α-MSH), a potent anti-inflammatory peptide, could prevent fulminant hepatic failure in mice. Acute liver damage was induced by intraperitoneal administration of thioacetamide. Hydrodynamics-based gene transfection with α-MSH expression plasmid via rapid tail vein injection was initiated 1 day prior to intoxication. The mortality in the α-MSH-treated mice was significantly lower compared to the vehicle group 3 days after injury. Liver histology significantly improved and TUNEL-positive hepatocytes decreased in the treated mice. The degradation of IκBα, endogenous inhibitor of nuclear factor κB, and upregulation of inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were prevented in the α-MSH-treated group, indicating decreased oxidative stress and inflammation. These results suggest α-MSH gene therapy might protect against acute hepatic necroinflammatory damage with further potential applications.

Original languageEnglish
Pages (from-to)153-161
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume322
Issue number1
DOIs
Publication statusPublished - Sep 10 2004
Externally publishedYes

Keywords

  • α-MSH
  • Fulminant hepatitis
  • Gene delivery
  • Thioacetamide

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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