Physiological linkage of gender, bioavailable hydroxytyrosol derivatives, and their metabolites with systemic catecholamine metabolism.

Despite extensive characterization of hydroxytyrosol (HT), there is a gap in the knowledge about its capacity to modulate catecholamine pathways. This study deals with the evaluation of the effects of HT, hydroxytyrosol acetate (HTA), and 3,4-dihydroxyphenylacetic acid (DOPAC), as well as their microbial metabolites (homovanillyl alcohol and tyrosol), on the excretion of catecholamines by UHPLC-ESI-QqQ-MS/MS upon administration at 1 and 5 mg kg-1 to male and female rats. The evaluation of urinary dopamine, norepinephrine, normetanephrine, and 3-methoxytyramine demonstrated 12.0- and 1.5-fold augmented excretions in males and females, respectively, due to the intake of HT derivatives. In addition, specific interconnections were identified between HT, HTA, DOPAC, and tyrosol and 3-methoxytyramine; between HTA and dopamine, norepinephrine, and normetanephrine; between HT, HTA, HVA, and tyrosol and dopamine, norepinephrine, and normetanephrine; and between HT, DOPAC, and HVA and dopamine and 3-methoxytyramine. Hence, a lack of linear relationships was observed between the oral administration of HT, HTA, and DOPAC and their plasma concentrations or urinary excretion levels after they were absorbed and distributed systemically. HT derivatives increase the synthesis of catecholamines in a derivative-, dosage-, and gender-dependent way.