Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice

R. Bruck*, H. Shirin, R. Hershkoviz, O. Lider, G. Kenet, H. Aeed, Z. Matas, L. Zaidel, Z. Halpern

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Background/Aims - It has been shown that synthetic non-peptidic analogues of Arg-Gly-Asp, a major cell adhesive ligand of extracellular matrix, prevented an increase in serum aminotransferase activity, as a manifestation of concanavalin A induced liver damage in mice. This study examined the effects of an Arg-Gly-Asp mimetic on liver histology and cytokine release in response to concanavalin A administration, and the efficacy of soluble receptor of tumour necrosis factor (TNF) or in preventing hepatitis in this model of liver injury. Methods - Mice were pretreated with either the Arg-Gly-Asp mimetic SF-6,5 or recombinant soluble receptor of TNFα before their inoculation with 10 mg/kg concanavalin A. Liver enzymes, histology, and the serum values of TNFα and interleukin (IL)6 were examined. Results - The histopathological damage in the liver, and the concanavalin A induced release of TNFα and IL6 were significantly inhibited by the synthetic Arg-Gly-Asp mimetic (p < 0.001). Liver injury, manifested by the increase in serum aminotransferase and cytokines, as well as by histological manifestations of hepatic damage, was effectively prevented by pretreatment of the mice with the soluble TNF receptor (p < 0.001). Conclusions - This study confirms the efficacy of a synthetic Arg-Gly-Asp mimetic and soluble TNF receptor in the prevention of immune mediated liver damage in mice.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalGut
Volume40
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Arg-Gly-Asp acid
  • Concanavalin A
  • Cytokines
  • Hepatitis
  • RGD mimetics
  • T lymphocytes

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