Diphenyl Diselenide Prevents Cortico-cerebral Mitochondrial Dysfunction and Oxidative Stress Induced by Hypercholesterolemia in LDL Receptor Knockout Mice

被引:38
作者
de Oliveira, Jade [1 ]
Gasnhar Moreira, Eduardo Luiz [1 ,2 ]
Mancini, Gianni [1 ]
Hort, Mariana Appel [1 ]
Latini, Alexandra [1 ]
Ribeiro-do-Valle, Rosa Maria [2 ]
Farina, Marcelo
Teixeira da Rocha, Joao Batista [3 ]
de Bem, Andreza Fabro [1 ]
机构
[1] Univ Fed Santa Catarina, Dept Bioquim, BR-88040900 Florianopolis, SC, Brazil
[2] Univ Fed Santa Catarina, Dept Farmacol, BR-88049900 Florianopolis, SC, Brazil
[3] Univ Fed Santa Maria, Dept Quim, BR-97105900 Santa Maria, RS, Brazil
关键词
Hypercholesterolemia; Oxidative stress; Mitochondrial dysfunction; Diphenyl diselenide; Low density lipoprotein receptor knockout mice; LOW-DENSITY-LIPOPROTEIN; VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; HIGH CHOLESTEROL; MILD HYPERCHOLESTEROLEMIA; ENERGY-METABOLISM; BLOOD-PRESSURE; TRACE AMOUNTS; NITRIC-OXIDE; BRAIN;
D O I
10.1007/s11064-013-1110-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2028 / 2036
页数:9
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