Nitroderivatives of olive oil phenols protect HepG2 cells against oxidative stress

A series of nitroderivatives has been synthetized from natural and synthetic olive oil phenols to increase the assortment of compounds with a putative effect against Parkinson disease. Before considering the potential therapeutical and nutraceutical applications of the new compounds it was critical to assess any cytotoxic effects in the liver. The precursor compounds of the nitroderivatives have shown oxidative stress protective effects, therefore we also assessed if the new compounds counteracted oxidative stress. The antioxidant activity of nitrohydroxytyrosol (NO-HTy), nitrohydroxytyrosyl-acetate (NO-HTy-A) and ethyl-nitrohydroxytyrosyl-ether (NO-HTy-E) at 5-20μM for 20. h, as well as the protective effects of the nitroderivatives after 20. h against oxidative stress induced by tert-butylhydroperoxide (t-BOOH), were assessed in HepG2 cells. Direct treatment with the three nitroderivatives decreased ROS generation compared to the control and NO-HTy at 20μM also increased glutathione peroxidase (GPx) activity (p<0.001). Pretreatment with the three nitroderivatives at 5-20μM counteracted t-BOOH cell damage by decreasing ROS generation (p < 0.001) and malondialdehyde (MDA) levels (p<0.001), increasing reduced glutathione (p<0.001) and disminishing GPx (p<0.05) activity. NO-HTy, NO-HTy-A and NO-HTy-E decreased glutathione reductase activity (p<0.05). Conclusion: the nitroderivatives do not present cytotoxic effects in the liver and in addition may protect against the oxidative stress involved in degenerative diseases. © 2012 Elsevier Ltd.This work was supported by the Grant AGR-5098 from the Junta de Andalucía and by Grants AGL2010-17579 and AGL2010-18269, and the CONSOLIDER INGENIO 2010 Programme; FUN-C-FOOD CSD2007-063 from the Spanish Ministry of Science and Innovation.Peer Reviewe