Non-peptidic analogs of the cell adhesion motif RGD prevent experimental liver injury.
In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic non-peptidic analogs of RGD in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and in inhibiting the development of liver cirrhosis in rats. The Con A-induced elevation of serum transaminases and tumor necrosis factor-alpha and the infiltration of liver tissue by inflammatory cells were inhibited by pretreatment of the mice with the synthetic RGD mimetics. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the co-administration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necro-inflammation and fibrosis.
Bruck
R
R
Department of Gastroenterology, Wolfson Medical Center, Holon, Israel. rafibruck@yahoo.com
Hershkoviz
R
R
Lider
O
O
Shirin
H
H
Aeed
H
H
Halpern
Z
Z
D000818:Animals; D002273:Carcinogens / Q000009:adverse effects; D003208:Concanavalin A / Q000009:adverse effects; D018450:Disease Progression; D006146:Guanidines / Q000627:therapeutic use; D019693:Hepatitis, Autoimmune / Q000473:pathology / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008934:Mitogens / Q000009:adverse effects; D009842:Oligopeptides / Q000819:agonists / Q000627:therapeutic use*; D051381:Rats; D011971:Receptors, Immunologic / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013853:Thioacetamide / Q000009:adverse effects; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014631:Valerates / Q000627:therapeutic use
D002273:Carcinogens; D006146:Guanidines; D008934:Mitogens; D009842:Oligopeptides; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D014631:Valerates; D013853:Thioacetamide; D003208:Concanavalin A; C084660:SF 6,5; C047981:arginyl-glycyl-aspartic acid; D000637:Transaminases