Interaction between allopurinol and copper: possible role in myocardial protection.
Allopurinol, a potent inhibitor of xanthine oxidase, is known to effectively protect the heart against damage in patients undergoing cardiac bypass surgery. There is still an ambiguity concerning the presence of xanthine oxidase in the human heart. Thus, the mechanism underlying the protective effect of allopurinol is unclear. Transition metal ions, such as iron and copper, can participate in single-electron reactions and mediate the formation of oxygen-derived free radicals. In this study the interaction between allopurinol and Cu(II) was investigated. Spectrophotometric investigation shows that allopurinol (0-0.8 mM) form a 1:1 complex with Cu(II) ions (0-0.8 mM) with a specific absorbance peak at 364 nm. Also, the rate constant (k) for the copper-catalyzed aerobic oxidation of ascorbate was markedly decreased in the presence of allopurinol (from 0.068 min-1 to 0.014 min-1). Allopurinol substantially reduced the copper-mediated and ascorbate-driven DNA breakage. Spectrophotometric measurements did not indicate a specific interaction between iron ions and allopurinol. It is suggested that the beneficial effects of allopurinol during reperfusion of the heart could stem from its chelation of copper, yielding a complex with low redox activity.
Malkiel
S
S
Department of Cellular Biochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
Har-el
R
R
Schwalb
H
H
Uretzky
G
G
Borman
J B
JB
Chevion
M
M
D000493:Allopurinol / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D015913:Chelation Therapy; D003300:Copper; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D006801:Humans; D007501:Iron; D007502:Iron Chelating Agents / Q000627:therapeutic use; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010084:Oxidation-Reduction
D007502:Iron Chelating Agents; D000493:Allopurinol; D003300:Copper; D007501:Iron; D001205:Ascorbic Acid