Peroxynitrite-mediated oxidation of fibrinogen inhibits clot formation

The clotting activity of human fibrinogen was fully inhibited in vitro by p eroxynitrite. The decrease of activity followed an exponential function and the concentration of peroxynitrite needed to inhibit 50% of fibrinogen clo tting was 22 mu M at 25 degrees C. The oxidative modification(s) induced by the peroxynitrite system (i.e. ONOO-, ONOOH and ONOOH*) appeared specifica lly to affect fibrin dot formation (through the inhibition of fibrinogen po lymerization) since the interaction of peroxynitrite-modified fibrinogen wi th thrombin appeared to be unaffected. The addition of NaHCO3 decreased the peroxynitrite effect on fibrinogen clotting, suggesting that the reactive species formed by the reaction of CO2 with peroxynitrite are less efficient oxidants of peroxynitrite itself, Similar effects were observed after addi tion of bilirubin, which also exerted a significant protection against pero xynitrite-mediated modification of fibrinogen. (C) 1999 Federation of Europ ean Biochemical Societies.