title: Diphenyl diselenide prevents cortico-cerebral mitochondrial dysfunction and oxidative stress induced by hypercholesterolemia in LDL receptor knockout mice.
abstract: Recent studies have indicated a causal link between high dietary cholesterol intake and brain oxidative stress. In particular, we have previously shown a positive correlation between elevated plasma cholesterol levels, cortico-cerebral oxidative stress and mitochondrial dysfunction in low density lipoprotein receptor knockout (LDLr(-/-)) mice, a mouse model of familial hypercholesterolemia. Here we show that the organoselenium compound diphenyl diselenide (PhSe)2 (1 mg/kg; o.g., once a day for 30 days) significantly blunted the cortico-cerebral oxidative stress and mitochondrial dysfunction induced by a hypercholesterolemic diet in LDLr(-/-) mice. (PhSe)2 effectively prevented the inhibition of complex I and II activities, significantly increased the reduced glutathione (GSH) content and reduced lipoperoxidation in the cerebral cortex of hypercholesterolemic LDLr(-/-) mice. Overall, (PhSe)2 may be a promising molecule to protect against hypercholesterolemia-induced effects on the central nervous system, in addition to its already demonstrated antiatherogenic effects.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Jade
authors.initials: J
authors.lastname: de Oliveira
authors.forename: Eduardo Luiz Gasnhar
authors.initials: EL
authors.lastname: Moreira
authors.forename: Gianni
authors.initials: G
authors.lastname: Mancini
authors.forename: Mariana Appel
authors.initials: MA
authors.lastname: Hort
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ribeiro-do-Valle
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006937:Hypercholesterolemia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011973:Receptors, LDL / Q000172:deficiency*
chemical_list: D001555:Benzene Derivatives; D002791:Cholesterol, Dietary; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D011973:Receptors, LDL; C061132:diphenyldiselenide; D002784:Cholesterol; D005979:Glutathione Peroxidase; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D005978:Glutathione