In vivo striatal measurement of hydroxytyrosol, and its metabolite (homovanillic alcohol), compared with its derivative nitrohydroxytyrosol.

Neurosci Lett

Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, 41012 Seville, Spain. Electronic address:

Published: September 2014

Phenolic compounds were measured by in vivo brain microdialysis in rat striatum. Basal extracellular levels of hydroxytyrosol, homovanillic alcohol and nitro-hydroxytyrosol were not detectable by HPLC with electrochemical detection. However, systemic administration of hydroxytyrosol (20 and 40mg/kg, i.p.) showed a clear increase in the extracellular level of this compound. This increase was accompanied by an increase in the extracellular level of homovanillic alcohol, a metabolite of hydroxytyrosol formed by catechol-O-methyltransferase activity. Perfusion of hydroxytyrosol (20μM) through the microdialysis cannula also produced an increase in the extracellular level of homovanillic alcohol. Systemic administration of nitro-hydroxytyrosol (20 and 40mg/kg, i.p.) produced a small increase in the extracellular level of this compound. Our data show that hydroxytyrosol is a more brain penetrant phenolic compound than nitro-hydroxytyrosol. Accordingly, there is high cerebral metabolism of hydroxytyrosol to produce homovanillic alcohol by catechol-O-methyltransferase activity, that is saturated at the higher administered dose of hydroxytyrosol.

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http://dx.doi.org/10.1016/j.neulet.2014.07.037DOI Listing

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