Aqueous cigarette tar extracts damage human alpha-1-proteinase inhibitor.
The elastase inhibitory capacity (EIC) of human alpha-1-proteinase inhibitor (alpha 1PI) is severely compromised by aqueous cigarette tar extract (ACTE). An aqueous extract of the tar from two cigarettes causes a loss of EIC of at least 60% in 24 h at 37 degrees C (pH 7.4) and the damaging capability of the ACTE is retained for many hours. Hydrogen peroxide appears to be an essential component of the mechanism by which ACTE damages alpha 1 PI, since catalase substantially protects alpha 1PI from ACTE-mediated damage. Only mild protection is offered by 10 mM diethylenetriamine pentaacetic acid, indicating only a minor role for transition metal ions in the alpha 1PI-damaging process. Hydroxyl radicals are unlikely agents of alpha 1PI damage in the ACTE system, as judged from hydroxyl radical scavenger studies. Ascorbate and various thiols offer protection to different degrees, dependent on the incubation conditions. Of several amino acids tested, cysteine and methionine (but not methionine sulfoxide) are the only two that protect alpha 1PI. We suggest that components of cigarette smoke particulate matter extracted into the aqueous lung fluid environment may cause local deficiencies in alpha 1PI in smokers' lungs.
Evans
M D
MD
Biodynamics Institute, Louisiana State University, Baton Rouge 70803.
Church
D F
DF
Pryor
W A
WA
D000596:Amino Acids / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D016166:Free Radical Scavengers; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D004369:Pentetic Acid / Q000494:pharmacology; D010947:Plants, Toxic; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012906:Smoke / Q000009:adverse effects*; D012995:Solubility; D013638:Tars / Q000009:adverse effects*; D014026:Nicotiana / Q000032:analysis*; D014867:Water; D000515:alpha 1-Antitrypsin / Q000187:drug effects*
D000596:Amino Acids; D000975:Antioxidants; D016166:Free Radical Scavengers; D006878:Hydroxides; D012906:Smoke; D013638:Tars; D000515:alpha 1-Antitrypsin; D014867:Water; D012710:Serum Albumin, Bovine; D004369:Pentetic Acid; C031356:hydroxide ion; D010196:Pancreatic Elastase; D005978:Glutathione; D004229:Dithiothreitol