Epicatechin selectively prevents nitration but not oxidation reactions of peroxynitrite

The flavanol (-)-epicatechin has been found to protect against damage infli cted by peroxynitrite, an inflammatory intermediate. Here, epicatechin was tested in systems of increasing complexity. The compound efficiently protec ted against nitration of protein tyrosine residues by peroxynitrite (IC50 a pproximate to 0.02 mol epicatechin/mol peroxynitrite). However, at epicatec hin concentrations completely preventing nitration of tyrosine by peroxynit rite, protection against the oxidative inactivation of glyceraldehyde-3-pho sphate dehydrogenase or soybean lipoxygenase-1 was marginal (IC50 > 1 mol e picatechin/mol peroxynitrite), approximately two orders of magnitude less. Likewise, epicatechin was relatively ineffective against oxidation of thiol s in cell lysates, and against the oxidation of 2 ' ,7 ' -dichlorodihydrofl uorescein in cultured cells. The activation of the kinases Akt/protein kina se B, ERK1/2 and p38-MAPK by peroxynitrite in murine aorta endothelial cell s was not altered by epicatechin, suggesting that activation of these kinas es is due to processes other than tyrosine nitration. (C) 2001 Academic Pre ss.