Diphenyl diselenide differently modulates cardiovascular redox responses in young adult and middle-aged low-density lipoprotein receptor knockout hypercholesterolemic mice.
OBJECTIVE
The present work aimed to investigate the effect of (PhSe)2 on cardiovascular age-related oxidative stress in hypercholesterolemic mice.


METHODS
To this end, LDL receptor knockout (LDLr(-/-) ) mice, 3 months (young adult) and 12 months (middle-aged) old, were orally treated with (PhSe)2 .


RESULTS
Hypercholesterolemia, regardless of age, impaired the mitochondrial antioxidant defence in the cardiac tissue, which was characterized by a decline in mitochondrial aortic glutathione (GSH) levels and increased reactive oxygen species production in the heart. (PhSe)2 treatment improved GSH levels, thioredoxin reductase (TRxR) and GSH reductase (GR) activity, and decreased malondialdehyde levels in the heart of young adult LDLr(-/-) mice. Moreover, (PhSe)2 increased GPx activity in both age groups, and GR activity in the aorta of middle-aged LDLr(-/-) mice.


CONCLUSIONS
Therefore, (PhSe)2 enhances the antioxidant defences in the cardiovascular system of LDLr(-/-) mice, which could explain its success as an anti-atherogenic compound.
Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Gianni
G
Mancini
Jade
J
de Oliveira
Mariana Appel
MA
Hort
Eduardo Luiz Gasnhar
EL
Moreira
Rosa Maria
RM
Ribeiro-do-Valle
João Batista Texeira
JB
Rocha
Andreza Fabro
AF
de Bem
D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001011:Aorta; D050197:Atherosclerosis / Q000517:prevention & control; D001555:Benzene Derivatives / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006937:Hypercholesterolemia / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances
D000975:Antioxidants; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D008315:Malondialdehyde; D005980:Glutathione Reductase; D005978:Glutathione
age; diphenyl diselenide; glutathione; hypercholesterolemia; oxidative stress