The antinephritic effects of
butein (3,4,2',4'-tetrahydroxychalcone) on original-type anti-glomerular basement membrane antibody-associated
glomerulonephritis in rats were investigated.
Butein was given to anti-glomerular basement membrane antibody-associated glomerulonephritic rats for 15 days after the induction of
nephritis.
Butein prevented
proteinuria and histological alterations. The up-regulation of
intercellular adhesion molecule-1 (ICAM-1) expression and increase in
leukocyte function-associated antigen-1 (LFA-1) positive cells in nephritic glomeruli significantly declined with
butein treatment. In the further investigation to clarify the effects of
butein on
ICAM-1 expression, human umbilical vein endothelial cells were treated with
butein in the presence of
tumor necrosis factor-alpha (
TNF-alpha) or
phorbol 12-myristate 13-acetate (PMA).
Butein prevented the up-regulation of
ICAM-1 expression mediated by
TNF-alpha or PMA on human umbilical vein endothelial cells in a dose-dependent manner. When human umbilical vein endothelial cells or neutrophils were treated with
butein, the adhesion of neutrophils to human umbilical vein endothelial cells was suppressed. These data suggest that the antinephritic action of
butein is due to inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of
ICAM-1 and the inhibition of a function of adhesion molecules on the surface of leukocytes.