TY - JOUR
T1 - Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice
AU - Bruck, R.
AU - Shirin, H.
AU - Hershkoviz, R.
AU - Lider, O.
AU - Kenet, G.
AU - Aeed, H.
AU - Matas, Z.
AU - Zaidel, L.
AU - Halpern, Z.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Arg-Gly-Asp acid
KW - Concanavalin A
KW - Cytokines
KW - Hepatitis
KW - RGD mimetics
KW - T lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=0031049463&partnerID=8YFLogxK
U2 - 10.1136/gut.40.1.133
DO - 10.1136/gut.40.1.133
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AN - SCOPUS:0031049463
SN - 0017-5749
VL - 40
SP - 133
EP - 138
JO - Gut
JF - Gut
IS - 1
ER -