title: Pyrrolidine dithiocarbamate is a potent antioxidant against hypochlorous acid-induced protein damage.
abstract: The antioxidant potential of the dithiol compound pyrrolidine dithiocarbamate (PDTC) against protein damage induced by hypochlorous acid (HOCl) was investigated. The effects of PDTC were compared to those of reduced glutathione (GSH) and N-acetylcysteine (NAC). PDTC markedly and in a concentration-dependent manner inhibited HOCl-induced inactivation of alpha(1)-antiproteinase, protein carbonyl formation on serum albumin and oxidation of human low-density lipoprotein. The direct scavenging of HOCl by PDTC was demonstrated by two quantitative methods, oxidation of ferrocyanide and chlorination of monochlorodimedon. In all assay systems, PDTC was two to three times more potent than GSH and NAC, while diethyldithiocarbamate was about as effective as PDTC. These data demonstrate that PDTC is a potent antioxidant against HOCl-induced protein oxidative damage, suggesting that PDTC might be useful in the prevention and treatment of inflammatory conditions.
authors.affiliation: Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331-6512, USA.
authors.forename: Ben-Zhan
authors.initials: BZ
authors.lastname: Zhu
authors.forename: Anitra C
authors.initials: AC
authors.lastname: Carr
authors.forename: Balz
authors.initials: B
authors.lastname: Frei
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002713:Chlorine / Q000378:metabolism; D003512:Cyclohexanones / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005295:Ferrocyanides / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors*; D008077:Lipoproteins, LDL / Q000378:metabolism; D016877:Oxidants / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D005295:Ferrocyanides; D008077:Lipoproteins, LDL; D016877:Oxidants; D011759:Pyrrolidines; D012709:Serum Albumin; D013859:Thiocarbamates; D000515:alpha 1-Antitrypsin; C099252:oxidized low density lipoprotein; C020972:pyrrolidine dithiocarbamic acid; D002713:Chlorine; D006997:Hypochlorous Acid; C006991:chlorodimedone; C020354:hexacyanoferrate II; D005978:Glutathione; D000111:Acetylcysteine