Diphenyl Diselenide Effectively Reduces Atherosclerotic Lesions in LDLr -/- Mice by Attenuation of Oxidative Stress and Inflammation

Glutathione peroxidase (GPx) plays an important role in the antioxidant defense of the vascular wall, and its deficiency has been implicated in the development of atherosclerotic lesions. This study analyzed the potential of diphenyl diselenide (DD), a simple organoselenium compound with GPx-like activity, to reduce atherosclerosis. Herein, we demonstrate that oral treatment with low doses of DD potently reduced the formation of atherosclerotic lesion in hypercholesterolemic low-density lipoprotein (LDL) receptor knockout (LDLr -/-) mice. This reduction was accompanied by significantly improved endothelium-dependent vasorelaxation, lower nitrotyrosine and malondialdehyde levels, decrease in vessel-wall infiltration by inflammatory cells, and prevention of upregulation of the proatherogenic monocyte chemoattractant protein-1. Studies in J774 macrophage-like cells show that DD significantly decreased oxLDL-induced formation of foam cells and the generation of reactive oxygen species and inflammatory mediators. Our results reveal the antiatherogenic actions of DD by modulating intracellular signaling pathways related to antioxidant and anti-inflammatory responses.