ANALYSIS OF ARG-GLY-ASP MIMETICS AND SOLUBLE RECEPTOR OF TUMOR-NECROSIS-FACTOR AS THERAPEUTIC MODALITIES FOR CONCANAVALIN-A INDUCED HEPATITIS IN MICE

Background/Aims-It has been shown that synthetic non-peptidic analogue s of Arg-Gly-Asp, a major cell adhesive ligand of extracellular matrix , prevented an increase in serum aminotransferase activity, as a manif estation of concanavalin A induced liver damage in mice. This study ex amined the effects of an Arg-Gly-Asp mimetic on liver histology and cy tokine release in response to concanavalin A administration, and the e fficacy of soluble receptor of tumour necrosis factor (TNF) alpha in p reventing hepatitis in this model of liver injury. Methods-Mice were p retreated with either the Arg-Gly-Asp mimetic SF-6,5 or recombinant so luble receptor of TNF alpha before their inoculation with 10 mg/kg con canavalin A. Liver enzymes, histology, and the serum values of TNF alp ha and interleukin (IL)6 were examined. Results-The histopathological damage in the Liver, and the concanavalin A induced release of TNF alp ha and IL6 were significantly inhibited by the synthetic Arg-Gly-Asp m imetic (p<0.001). Liver injury, manifested by the increase in serum am inotransferase and cytokines, as well as by histological manifestation s of hepatic damage, was effectively prevented by pretreatment of the mice with the soluble TNF receptor (p<0.001). Conclusions-This study c onfirms the efficacy of a synthetic Arg-Gly-Asp mimetic and soluble TN F receptor in the prevention of immune mediated liver damage in mice.