Diphenyl diselenide differently modulates cardiovascular redox responses in young adult and middle-aged low-density lipoprotein receptor knockout hypercholesterolemic mice

Objectives 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. Key findings 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.