Amelioration of hepatic inflammation in a mouse model of NASH using a dithiocarbamate derivative

Jason J. Schwartz*, Lyska Emerson, Elaine Hillas, Ann Phan, Heather Thiesset, Matthew Firpo, Jeffrey Sorensen, Thomas Kennedy, Mary Rinella

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Purpose: The process whereby liver inflammation develops in non-alcoholic steatohepatitis (NASH) is not fully understood. While modification of the inflammatory milieu is an attractive target to prevent the development of hepatocellular injury, most antiinflammatory agents have proven ineffective in this setting. Tetraethylthiuram disulfide (TDSF) is able to induce S-glutathionylation of NF-κB along with critical signaling proteins involved with inflammation, especially when complexed with a heavy metal. For this reason, we hypothesized that administration of TDSF would function to ameliorate necroinflammatory activity in a mouse model of NASH. Methods: Mice were divided into five groups and received control chow versus a methionine-choline-deficient diet. After 6 weeks of TDSF versus sham gavage, animals were necropsied. Using conventional H&E staining, livers were examined using the Brunt scoring system by a hepatopathologist blinded to treatment groups. Validated mouse primer sets were used for quantitative real-time PCR to evaluate changes in mRNA expression. Results: Livers treated with TDSF demonstrated a qualitative reduction in lobular inflammation, lipogranuloma formation, and Kupffer cell accumulation, but not steatosis. Significant reductions in inflammatory transcripts for α-1-collagen, TGF-β, Mmp2, MCP-1, and TNF-1α were also observed. Conclusions: Animals treated with TDSF exhibit a reduction in lobular inflammation that is independent of lipid accumulation when administered MCD diet. Similar reductions are seen in several inflammatory transcripts associated with NASH. Additional work in this area may reveal a therapeutic role for TDSF or similar agents in curtailing inflammatory signaling within the liver.

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalHepatology International
Volume7
Issue number2
DOIs
StatePublished - Jun 1 2013

Keywords

  • Animal Models
  • Disulfiram
  • Dithiocarbamates
  • NAFLD
  • NASH
  • Therapies

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Amelioration of hepatic inflammation in a mouse model of NASH using a dithiocarbamate derivative'. Together they form a unique fingerprint.

Cite this