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

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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

Fingerprint

Thioacetamide
Melanocyte-Stimulating Hormones
Acute Liver Failure
Liver
Plasmids
Injections
Oxidative stress
Oxidative Stress
Gene transfer
Gene therapy
Histology
In Situ Nick-End Labeling
Wounds and Injuries
Corrosion inhibitors
Nitric Oxide Synthase Type II
Hydrodynamics
Genetic Therapy
Genes
Transfection
Tail

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Single injection of naked plasmid encoding α-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice. / Wang, Cheng Haung; Jawan, Bruno; Lee, Tsung Hsing; Hung, Kuo Sheng; Chou, Wen Ying; Lu, Cheng Nann; Liu, Jong Kang; Chen, Yann Jang.

In: Biochemical and Biophysical Research Communications, Vol. 322, No. 1, 10.09.2004, p. 153-161.

Research output: Contribution to journalArticle

Wang, Cheng Haung ; Jawan, Bruno ; Lee, Tsung Hsing ; Hung, Kuo Sheng ; Chou, Wen Ying ; Lu, Cheng Nann ; Liu, Jong Kang ; Chen, Yann Jang. / Single injection of naked plasmid encoding α-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 322, No. 1. pp. 153-161.
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