Hydroxytyrosol induces phase II detoxifying enzyme expression and effectively protects dopaminergic cells against dopamine- and 6-hydroxydopamine induced cytotoxicity

•Hydroxytyrosol (HT) protects SH-SY5Y cells from DA and 6-OHDA induced cell death.•HT pretreatment has no effect on MPP+-induced cell death.•HT treatment increases the expression of several phase II enzymes.•NQO1 contributed to the protective effect of HT against dopaminergic cell death.

Parkinson's disease (PD) is the second most common late-age onset neurodegenerative disease. Except for the symptomatic alleviating treatment, no disease modifying therapy is currently available. In this study, we investigated the potential neuroprotective role of hydroxytyrosol (HT), a major phenolic compound present in olive oil, against dopaminergic cell death. We found that HT effectively protected dopaminergic SH-SY5Y cells against dopamine (DA) and 6-hydroxydopamine (6-OHDA) induced cell death, but had no apparent effect on 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity. Furthermore, we have shown that HT efficiently induced the expression of phase II detoxifying enzymes, including NAD(P)H quinone oxidoreductase 1 (NQO1). Using an NQO1 inhibitor, we revealed that increased NQO1 expression contributed to the protective effect of HT against dopaminergic cell death. Together, our findings suggest that HT has a protective effect against DA- and 6-OHDA-induced dopaminergic cell death, supporting the beneficial effect of olive oil in preventing DA-metabolism related dopaminergic neuron dysfunction.