A Diet Rich in Olive Oil Phenolics Reduces Oxidative Stress in the Heart of SAMP8 Mice by Induction of Nrf2-Dependent Gene Expression

Abstract

A Mediterranean diet rich in olive oil has been associated with health benefits in humans. It is unclear if and to what extent olive oil phenolics may mediate these health benefits. In this study, we fed senescence-accelerated mouse-prone 8 (SAMP8, n = 11 per group) semisynthetic diets with 10% olive oil containing either high (HP) or low amounts of olive oil phenolics (LP) for 4.5 months. Mice consuming the HP diet had significantly lower concentrations of the oxidative damage markers thiobarbituric acid-reactive substances and protein carbonyls in the heart, whereas proteasomal activity was similar in both groups. Nrf2-dependent gene expression may be impaired during the aging process. Therefore, we measured Nrf2 and its target genes glutathione-S-transferase (GST), c-glutamyl cysteine synthetase (c-GCS), nicotinamide adenine dinucleotide phosphate [NAD(P)H]:quinone oxidoreductase (NQO1), and paraoxonase-2 (PON2) in the hearts of these mice. Nrf2 as well as GST, c-GCS, NQO1, and PON2 mRNA levels were significantly higher in heart tissue of the HP as compared to the LP group. The HP-fed mice had significantly higher PON1 activity in serum compared to those receiving the LP diet. Furthermore, HP feeding increased relative SIRT1 mRNA levels. Additional mechanistic cell culture experiments were performed, and they suggest that the olive oil phenolic hydroxytyrosol present in the HP oil may be responsible for the induction of Nrf2-dependent gene expression and the increase in PON activity. In conclusion, a diet rich in olive oil phenolics may prevent oxidative stress in the heart of SAMP8 mice by modulating Nrf2-dependent gene expression.

Amelioration of oxidative and inflammatory status in hearts of cholesterol-fed rats supplemented with oils or oil-products with extra virgin olive oil components

“…Our results are in line with other studies where rats supplemented with olive phenolics presented decreased heart MDA content [38]. Moreover, in SAMP8 mice fed on a diet rich in olive oil phenolics, oxidative stress in heart was prevented [42]. On the other hand, EVOO(−), SO, and HOSO did not lower hypercholesterolemia-caused lipid peroxidation in heart.…”

Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential

“…(4). This hypothesis is supported by a very recent study in vivo, showing that a diet rich in olive oil phenols reduced oxidative stress in the heart of senescence-accelerated mouse-prone 8 mice by the induction of Nrf2-dependent gene expression [88].…”

Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression

“…Changes in gene expression indicate that the anti-inflammatory profile involves phospholipase and inflammatory pathways. There was very little evidence that changes in gene expression relating to the phase II enzymes and the Nrf2 canonical pathway were altered by OLE consumption, although inhibition of this pathway by olive oil phenolics has been suggested as instrumental in oxidative and inflammatory protection [6,7]. Many of the downregulated genes are pivotal in inflammation and disease ( OSM , COX-2 and IL-8 ).…”

“…These studies showed altered expression of genes in relevant pathways. Animal [6] and in vitro [7] models have pointed towards interactions with Nrf2 (Nuclear factor erythroid 2-related factor 2) signalling cascades as one effector for the health benefits of polyphenols. However, this hypothesis has not been substantiated in human trials [8].…”