Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats

Abstract

Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims , being the only authorized health claim in the European Union regarding polyphenols and health.

Oxidative Status and Presence of Bioactive Compounds in Meat from Chickens Fed Polyphenols Extracted from Olive Oil Industry Waste

“…Identification studies carried out with the authentic standards revealed that both isomers (hydroxytyrosol-3-sulphate and hydroxytyrosol-4-sulphate) were present (data not shown). It must be underlined that most of the previous studies [18][19][20]41] were performed measuring polyphenols and their metabolites immediately after the administration of high doses of polyphenols. To the best of our knowledge, to date no research has reported residue levels of these compounds in meat of food-producing animals within an on-farm trial.…”

“…However, these techniques are still used to analyze polyphenols in food of animal and vegetal origin [16,17]. Sample preparation plays a pivotal role in polyphenol analysis, especially when low concentrations (parts per billions) have to be detected and quantified: a clean-up step with SPE cartridges is generally provided after analyte extraction with polar solvents [18][19][20].…”

Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders

“…Granados-Principal et al [106] found in cardiac tissue that HT (0.5 mg/kg, 5 days/week × 6 weeks) increases expression of mitochondria complexes 1, 2 and 3 and reduces specific markers of oxidative damages to proteins. These HT beneficial effects on cardiac function are probably due to its antioxidative properties (0.1 and 10 µg/mL) [109], since HT was not found in rat heart (1, 10 and 100 mg/kg) [138]. …”

3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in Spontaneous Oxidation of Dopamine During Monoamine Oxidase Inhibition in PC12 Cells

“…Because DOPET is a neutral alcohol, exogenously administered DOPET would be expected to diffuse readily within the total body water space and enter central neurons; and because DOPET is a catechol, intracellular DOPET would be expected to act as an anti-oxidant. Consistent with these expectations, oral administration of DOPET to rats results in dose-related increases in brain tissue levels of DOPET and its metabolites [15], and after systemic injection DOPET is detected in striatal microdialysate [16]. Systemically administered DOPET prevents the increases in lipid peroxides and the decreases in reduced glutathione levels in striatum that are evoked by 3-nitropropionic acid [17], indicating an ability to exert anti-oxidant effects in central dopaminergic neurons.…”