title: Apparent inactivation of alpha 1-antiproteinase by sulphur-containing radicals derived from penicillamine.
abstract: alpha 1-Antiproteinase is the major inhibitor of proteolytic enzymes, such as elastase, in human plasma. Its elastase-inhibitory capacity can be inactivated by exposure to hydroxyl radicals (.OH) generated either by pulse radiolysis or by an Fe3+-EDTA/H2O2/ascorbic acid system. Inactivation of alpha 1-antiproteinase by radiolytically-generated .OH under anoxic conditions was decreased by adding a range of anti-inflammatory drugs to the reaction mixtures, including the thiol compound penicillamine. However, under conditions favouring formation of oxysulphur radicals, protection by thiols such as penicillamine was much decreased. It is proposed that sulphur-containing radicals resulting from attack of biologically-produced oxidants upon penicillamine in the presence of O2 can themselves inactivate alpha 1-antiproteinase, and that such radicals might contribute to the side-effects produced by penicillamine or gold thiol therapy in rheumatoid arthritis.
authors.affiliation: Department of Biochemistry, University of London King's College, U.K.
authors.forename: O I
authors.initials: OI
authors.lastname: Aruoma
authors.forename: B
authors.initials: B
authors.lastname: Halliwell
authors.forename: J
authors.initials: J
authors.lastname: Butler
authors.forename: B M
authors.initials: BM
authors.lastname: Hoey
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D006801:Humans; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D010196:Pancreatic Elastase / Q000378:metabolism; D010396:Penicillamine / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000032:analysis* / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006878:Hydroxides; D000515:alpha 1-Antitrypsin; D017665:Hydroxyl Radical; D010196:Pancreatic Elastase; D010396:Penicillamine