Oxidative damage to lipids and alpha 1-antiproteinase by phenylbutazone in the presence of haem proteins: protection by ascorbic acid.
Phenylbutazone is an anti-inflammatory drug with numerous side-effects that restrict its clinical use. In the presence of myoglobin, or of haemoglobin plus H2O2, phenylbutazone accelerates the peroxidation of lipids (arachidonic acid and rat liver microsomes) and causes the inactivation of alpha-antiproteinase, so that this protein can no longer inhibit elastase. We propose that haem proteins oxidize phenylbutazone into a damaging free radical. Ascorbic acid inhibits these pro-oxidant actions of phenylbutazone.
Evans
P J
PJ
Department of Biochemistry, University of London Kings College, U.K.
Cecchini
R
R
Halliwell
B
B
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005609:Free Radicals; D006420:Hemeproteins / Q000378:metabolism*; D050356:Lipid Metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010653:Phenylbutazone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D005609:Free Radicals; D006420:Hemeproteins; D009211:Myoglobin; D000515:alpha 1-Antitrypsin; D016718:Arachidonic Acid; D010653:Phenylbutazone; D001205:Ascorbic Acid