Non-peptidic analogs of the cell adhesion motif RGD prevent experimental liver injury.

Abstract

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.

• Authors: R Bruck, R Hershkoviz, O Lider, H Shirin, H Aeed, Z Halpern
• Journal: The Israel Medical Association journal : IMAJ (Isr Med Assoc J) Vol. 2 Suppl Pg. 74-80 (Jul 2000) ISSN: 1565-1088 [Print] Israel
• PMID: 10909422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carcinogens
• Guanidines
• Mitogens
• Oligopeptides
• Receptors, Immunologic
• Tumor Necrosis Factor-alpha
• Valerates
• Thioacetamide
• Concanavalin A
• SF 6,5
• arginyl-glycyl-aspartic acid
• Transaminases

Topics

• Animals
• Carcinogens (adverse effects)
• Concanavalin A (adverse effects)
• Disease Progression
• Guanidines (therapeutic use)
• Hepatitis, Autoimmune (pathology, prevention & control)
• Liver Cirrhosis, Experimental (pathology, prevention & control)
• Mice
• Mitogens (adverse effects)
• Oligopeptides (agonists, therapeutic use)
• Rats
• Receptors, Immunologic (drug effects)
• T-Lymphocytes (drug effects, immunology)
• Thioacetamide (adverse effects)
• Transaminases (blood)
• Tumor Necrosis Factor-alpha (analysis)
• Valerates (therapeutic use)