In vivo distribution and deconjugation of hydroxytyrosol phase II metabolites in red blood cells: A potential new target for hydroxytyrosol

Olive oil phenolic compounds are extensively metabolized into methylated and glucurono- and sulpho-conjugates of hydroxytyrosol (HT), the detected circulating forms in plasma. However, these conjugates are considered to be pharmacologically inactive and their in situ deconjugation in certain sites appears to be an absolute requirement to exert their beneficial effects. In the present study, red blood cells (RBCs) were analysed in rats after an oral administration of an olive phenolic extract and their in vivo deconjugation capacity of hydroxytyrosol phase II metabolites was assessed. A decreasing trend of the conjugated forms of HT and a parallel free HT increasing in concentration up to 6 h was observed in RBCs, indicating that HT conjugates might be hydrolysed intracellularly in RBCs. Our results suggest that RBCs could play a pivotal role in the distribution and bioavailability of circulating phenols and their metabolites and also in protection against oxidative damage to cells.