BUTEIN (3,4,2',4'-TETRAHYDROXYCHALCONE) AMELIORATES EXPERIMENTAL ANTIGLOMERULAR BASEMENT-MEMBRANE ANTIBODY-ASSOCIATED GLOMERULONEPHRITIS .3.

The antinephritic effects of butein (3,4,2',4'-tetrahydroxychalcone) o n original-type anti-glomerular basement membrane antibody-associated glomerulonephritis in rats were investigated. Butein was given to anti -glomerular basement membrane antibody-associated glomerulonephritic r ats for 15 days after the induction of nephritis. Butein prevented pro teinuria and histological alterations. The up-regulation of intercellu lar adhesion molecule-1 (ICAM-1) expression and increase in leukocyte function-associated antigen-1 (LFA-I) positive cells in nephritic glom eruli significantly declined with butein treatment. In the further inv estigation to clarify the effects of butein on ICAM-1 expression, huma n umbilical vein endothelial cells were treated with butein in the pre sence of tumor necrosis factor-alpha (TNF-alpha) or phorbol 12-myrista te 13-acetate (PMA). Butein prevented the up-regulation of ICAM-1 expr ession mediated by TNF-alpha or PMA on human umbilical vein endothelia l cells in a dose-dependent manner. When human umbilical vein endothel ial cells or neutrophils were treated with butein, the adhesion of neu trophils to human umbilical vein endothelial cells was suppressed. The se data suggest that the antinephritic action of butein is due to inhi bition of intraglomerular accumulation of leukocytes through the preve ntion of the up-regulation of ICAM-1 and the inhibition of a function of adhesion molecules on the surface of leukocytes.