title: Diphenyl diselenide effectively reduces atherosclerotic lesions in LDLr -/- mice by attenuation of oxidative stress and inflammation.
abstract: 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.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Mariana Appel
authors.initials: MA
authors.lastname: Hort
authors.forename: Marcos Raniel
authors.initials: MR
authors.lastname: Straliotto
authors.forename: Paula Moro
authors.initials: PM
authors.lastname: Netto
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ribeiro-do-Valle
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001555:Benzene Derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D018836:Inflammation Mediators / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011897:Random Allocation; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics
chemical_list: D000975:Antioxidants; D001555:Benzene Derivatives; D018836:Inflammation Mediators; D016566:Organoselenium Compounds; D011973:Receptors, LDL; C061132:diphenyldiselenide