Hydroxytyrosol glucuronides protect renal tubular epithelial cells against H₂O₂ induced oxidative damage

• Published in: Chemico-biological interactions Vol. 193; no. 3; pp. 232 - 239
• Main Authors: Deiana, Monica, Incani, Alessandra, Rosa, Antonella, Atzeri, Angela, Loru, Debora, Cabboi, Barbara, Paola Melis, M, Lucas, Ricardo, Morales, Juan C, Assunta Dessì, M
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 30.09.2011
• Subjects: cell death; cell viability; epithelial cells; ethanol; fatty acids; hydrogen peroxide; hydroperoxides; kidneys; lipid peroxidation; malondialdehyde; metabolites; mitogen-activated protein kinase; olive oil; phosphorylation; protective effect; signal transduction; swine; toxicity
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2011.07.002

Hydroxytyrosol (2-(3′,4′-dihydroxyphenyl)ethanol; HT), the most active ortho-diphenolic compound, present either in free or esterified form in extravirgin olive oil, is extensively metabolized in vivo mainly to O-methylated, O-sulfated and glucuronide metabolites. We investigated the capacity of three glucuronide metabolites of HT, 3′-O-β-d-glucuronide and 4′-O-β-d-glucuronide derivatives and 2-(3′,4′-dihydroxyphenyl)ethanol-1-O-β-d-glucuronide, in comparison with the parent compound, to inhibit H₂O₂ induced oxidative damage and cell death in LLC-PK1 cells, a porcine kidney epithelial cell line. H₂O₂ treatment exerted a toxic effect inducing cell death, interacting selectively within the pro-death extracellular-signal relate kinase (ERK 1/2) and the pro-survival Akt/PKB signaling pathways. It also produced direct oxidative damage initiating the membrane lipid peroxidation process. None of the tested glucuronides exhibited any protection against the loss in renal cell viability. They also failed to prevent the changes in the phosphorylation states of ERK and Akt, probably reflecting their inability to enter the cells, while HT was highly effective. Notably, pretreatment with glucuronides exerted a protective effect at the highest concentration tested against membrane oxidative damage, comparable to that of HT: the formation of malondialdehyde, fatty acid hydroperoxides and 7-ketocholesterol was significantly inhibited.