ANTIOXIDANT ACTIVITY OF PROPYLTHIOURACIL

Propylthiouracil (PTU) has been demonstrated to reduce alcohol-induced hepatocyte damage and severe alcoholic liver disease. Although the mechanism by which the drug operates is yet to be elucidated, there is evidence that PTU may act as an antioxidant. The present study examines the reaction of PTU with oxygen free radicals and the ability of PTU to directly inhibit peroxidation of a model membrane system. PTU reacted directly with hydroxyl radicals produced by gamma-radiolysis. The rate constant for the PTU/hydroxyl radical reaction as determined by steady state competition kinetics with p-nitrosodimethylaniline was 8 x 10(9) L/mol/sec. PTU was less reactive towards superoxide generated by the xanthine/xanthine oxidase system, having a small but significant inhibitory effect on superoxide-induced reduction of cytochrome c only at a concentration of 200-mu-M. The ability of PTU to protect lipids from peroxidative changes was tested in membranes prepared from linoleic acid. The rate of peroxidation induced by 40-degrees heat decreased from 0.078 to 0.024 mM hydroperoxide/hr in the presence of 0-50-mu-M PTU. However, this trend was reversed at PTU concentrations above 50-mu-M. These data suggest that the protective effects of PTU against liver damage may be due to scavenging reactions with hydroxyl radicals in particular and/or its antioxidant potential.