Thiols and disulphides can aggravate peroxynitrite-dependent inactivation of alpha(1)-antiproteinase

Peroxynitrite (ONOO-) is a cytotoxic species formed in vivo, There is considerable interest in the development of ONOO- 'scavengers' as therapeutic agents; several thiols have been suggested to fulfil this role, One protein inactivated by ONOO- is alpha(1)-antiproteinase (alpha(1)AP), the major inhibitor of serine proteinases in human body fluids, At low thiol:ONOO- concentration ratios, several thiols (captopril, penicillamine, cysteine, cystine and penicillamine disulphide) aggravated inactivation of alpha(1)AP by ONOO-, whereas GSH, GSSG, homocysteine, ergothioneine, N-acetylcysteine, lipoate and dihydrolipoate did not, We suggest that sulphur-containing radicals are produced by reaction of certain thiols/disulphides with ONOO- or ONOO--derived products and could mediate biological damage, including inactivation of alpha(1)AP. This must be considered in attempts to use thiols as 'peroxynitrite scavengers'. (C) 1997 Federation of European Biochemical Societies.