Dose effect on the uptake and accumulation of @entity36719 and its metabolites in target tissues in XXXX .

@entity1 @entity8 @entity566 @entity409 @entity36719 @entity35 @entity6398 @entity65
@entity36719 (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 @entity65 prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in @entity35 , and thus, providing complementary information in relation to the target-dose relationship. @entity35 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 @entity1 doses. The detection of free @entity409 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 @entity8 . 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 @entity566 (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil @entity6398 and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil @entity6398 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 @entity6398 and health.
