Article

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

Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
Rejuvenation Research (Impact Factor: 3.31). 02/2012; 15(1):71-81. DOI: 10.1089/rej.2011.1245
Source: PubMed

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), γ-glutamyl cysteine synthetase (γ-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, γ-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.

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    • "Olive oil, the primary source of fat in the Mediterranean diet, has been suggested to have potential antioxidant (Turner et al., 2010), antiinflammatory (Zhang, Cao, & Zhong, 2009), cardioprotective (Bayram et al., 2012), anticancer (Gill et al., 2005), antidiabetic (Rigacci et al., 2010) and neuroprotective activity (Schaffer et al., 2007). Olive oil is characterized by a high content of oleic acid and is an important source of hydrophilic phenolic compounds that contribute to stability, sensory, technological, and nutritional properties of olive oil (Servili et al., 2004). "

    Full-text · Dataset · Jul 2015
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    • "Olive oil, the primary source of fat in the Mediterranean diet, has been suggested to have potential antioxidant (Turner et al., 2010), antiinflammatory (Zhang, Cao, & Zhong, 2009), cardioprotective (Bayram et al., 2012), anticancer (Gill et al., 2005), antidiabetic (Rigacci et al., 2010) and neuroprotective activity (Schaffer et al., 2007). Olive oil is characterized by a high content of oleic acid and is an important source of hydrophilic phenolic compounds that contribute to stability, sensory, technological, and nutritional properties of olive oil (Servili et al., 2004). "

    Full-text · Dataset · Jul 2015
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    • "Claims of the antioxidant activity of HT are prevalent in the literature. Early in vitro studies suggested that HT was a direct acting antioxidant, scavenging oxidative species by chemical interaction, however, more recent investigation in mice and human cell lines suggests that HT may instead act through activation of the antioxidant response element (ARE) promoter region, which facilitates transcription of Phase II enzymes that are active in the detoxification of oxidatively insulting species (Bayram et al., 2012; Zou et al., 2012). HT has also been demonstrated to protect against oxidative damage and disturbance in the mitochondria of rats subjected to doxorubicin-induced cardiotoxicity in a breast cancer model (Granados-Principal et al., 2014), presumably through the anti-oxidant properties of HT, and to also protect against endoplasmic reticulum stress (ER stress) in a tunicamycin-induced model of ER stress in the HepG2 liver cancer cell line (Giordano et al., 2014). "
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    ABSTRACT: The safety of olive extract H35 containing 35% hydroxytyrosol (HT) was tested in a 90-day oral gavage study in Wistar rats. H35 was administered at 0, 345, 691 and 1381 mg/kg bw/day, equivalent to 0, 125, 250 and 500 mg HT/kg bw/day. Reductions in terminal body weight (9%), and a statistically significant reduction in body weight gain (17%, P<0.05) at week 13 were observed in high dose males, as well as a statistically significant increase in relative weights of the liver, heart, and kidneys of high dose males and females. These changes were not accompanied by pathological or clinical observations and a trend towards reversal was observed in the recovery phase. H35 was well-tolerated and no toxicologically significant treatmentrelated changes were observed in condition and appearance of rats, neurobehavioral outcomes, motor activity assessments, functional observational battery (FOB), food intake, ophthalmoscopic examinations, hematology, clinical chemistry, urinalysis, necropsy findings, sperm parameters or estrus cycle. The lowest observed adverse effect level (LOAEL) was the 500 mg HT/kg bw/day based on statistically significant reductions in body weight gain and decreased body weight in males. The no observed adverse effect level (NOAEL) was 250 mg HT/kg bw/day, equivalent to 691 mg/kg bw/day of H35 extract. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
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