Probucol Protects Arteries by Inhibiting Two-Electron Oxidant

The models comprised apolipoprotein E–deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Animals in each group were treated with probucol, its sulfur-containing metabolite, or a sulfur-free phenolic analogue.

Results published in the April 10, 2006, online edition of the Journal of Experimental Medicine showed that probucol and its sulphur-containing metabolite, but not the sulphur-free phenolic analogue, protected the arteries via cell-specific effects on inhibiting macrophage accumulation, stimulating re-endothelialization, and inhibiting vascular smooth muscle cell proliferation. These effects were found to be mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E.

The authors concluded that, "Two-electron rather than radical [one-electron] oxidants are important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.”



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