Antioxidant activity of allopurinol on copper-catalysed human lipoprotein oxidation.
We found that allopurinol, at therapeutically relevant concentrations (9-58 microM), significantly counteracted copper-catalysed human non-HDL lipoprotein oxidation, as assessed by thiobarbituric acid reactant content and kinetics of conjugated diene formation. Oxypurinol was ineffectual. Both drugs had no activity on metal-independent, peroxyl radical-induced lipoprotein oxidation. Specific fluorescence-quenching experiments revealed that only allopurinol could interact with copper antagonizing metal binding to lipoproteins. Thus, therapeutic allopurinol concentrations can inhibit copper-catalysed lipoprotein oxidation through metal complexation, suggesting some antioxidant-antiatherogenic activity of the drug in vivo.
Lapenna
D
D
Istituto di Fisiopatologia Medica, Università degli Studi G. D'Annunzio, Facoltà di Medicina e Chirurgia, Chieti, Italy.
de Gioia
S
S
Ciofani
G
G
Cuccurullo
F
F
D000328:Adult; D000493:Allopurinol / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002384:Catalysis; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000494:pharmacology
D000975:Antioxidants; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D000493:Allopurinol; D003300:Copper; D010117:Oxypurinol