Peroxynitrite formation in vivo is implicated in numerous human diseases and there is considerable interest in the use of antioxidants and natural products Such as thiols as "peroxynitrite scavengers". We therefore investigated the effects of a recently identified constituent of onions, 3-mercapto-2-methylpentan-1-ol (3-MP), for its ability to inhibit peroxynitrite-mediated processes in vitro and using cultured human cells and compared its effectiveness against glutathione. 3-MP significantly inhibited peroxynitrite-mediated tyrosine nitration and inactivation of alpha(1)-antiproteinase to a greater extent than glutathione at each concentration tested ( 15-500 muM). 3-MP also inhibited peroxynitrite-induced cytotoxicity, intracellular tyrosine nitration, and intracellular reactive oxygen species generation in human HepG2 cells in Culture to a greater extent than glutathione. These data suggest that 3-MP has the potential to act as an inhibitor of ONOO--mediated processes in vivo and that the antioxidant action of 3-MP deserves further study. (C) 2003 Elsevier Science (USA). All rights reserved.