title: Diphenyl diselenide modulates oxLDL-induced cytotoxicity in macrophage by improving the redox signaling.
abstract: It has been reported that oxidized LDLs (oxLDL) are involved in the pathogenesis of atherosclerosis, and that macrophages as well as other cells of the arterial wall can oxidize LDL in vitro, depending on the balance between intracellular prooxidant generation and antioxidant defense efficiency. Because of their potential beneficial role in preventing atherosclerosis and other oxidative stress-related diseases, organoselenium compounds such as diphenyl diselenide (PhSe)2, are receiving increased attention. In the present work, we investigated the mechanisms underlying the protective effect exerted by (PhSe)2 on oxLDL-mediated effects in murine J774 macrophage-like cells. (PhSe)2 pretreatment reduced atherogenic signaling triggered by oxLDL in macrophages in vitro, namely: ROS generation, disturbance of NO homeostasis, activation of matrix metalloproteinase, foam cell formation, and mitochondrial dysfunction. Moreover, the redox signaling effects of (PhSe)2 presented herein were accompanied by a downregulation of NF-κB-binding activity. The relatively strong performance of (PhSe)2 makes it an ideal candidate for further, expanded trials as a new generation of antioxidants for preventing atherosclerotic lesion.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Marcos Raniel
authors.initials: MR
authors.lastname: Straliotto
authors.forename: Mariana Appel
authors.initials: MA
authors.lastname: Hort
authors.forename: Bianca
authors.initials: B
authors.lastname: Fiuza
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: Rocha
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Gustavo
authors.initials: G
authors.lastname: Chiabrando
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008077:Lipoproteins, LDL / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001555:Benzene Derivatives; D008077:Lipoproteins, LDL; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C061132:diphenyldiselenide; D020781:Matrix Metalloproteinase 1