Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia-reoxygenation

Neurosci Lett. 2008 Dec 3;446(2-3):143-6. doi: 10.1016/j.neulet.2008.09.022.

Abstract

Hydroxytyrosol (HT) and hydroxytyrosol acetate (HT-AC) are two well-known phenolic compounds with antioxidant properties that are present in virgin olive oil (VOO). Because VOO has shown neuroprotective effects in rats, the purpose of the present study was to investigate the possible neuroprotective effect of HT and HT-AC in a model of hypoxia-reoxygenation in rat brain slices after in vitro incubation of these compounds or after 7 days of oral treatment with 5 or 10 mg/kg per day. Lactate dehydrogenase (LDH) efflux to the incubation medium was measured as a marker of brain cell death. HT and HT-AC inhibited LDH efflux in a concentration-dependent manner, with 50% inhibitory concentrations of 77.78 and 28.18 microM, respectively. Other well-known antioxidants such as vitamin E and N-acetyl-cysteine had no neuroprotective effect in this experimental model. After 1 week of treatment, HT (5 and 10 mg/kg per day p.o.) reduced LDH efflux by 37.8% and 52.7%, respectively, and HT-AC reduced LDH efflux by 45.4% and 67.8%. These data are additional evidence of the cytoprotective effect of VOO administration, and provide a preliminary basis for further study of these polyphenols as potential neuroprotective compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Acetates / therapeutic use
  • Animals
  • Antioxidants / pharmacology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Catechols / pharmacology*
  • Catechols / therapeutic use
  • Diet, Mediterranean
  • Dose-Response Relationship, Drug
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / physiopathology
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neuroprotective Agents / pharmacology*
  • Olive Oil
  • Organ Culture Techniques
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Phenylethyl Alcohol / therapeutic use
  • Plant Oils / therapeutic use
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology

Substances

  • Acetates
  • Antioxidants
  • Catechols
  • Neuroprotective Agents
  • Olive Oil
  • Plant Oils
  • hydroxytyrosyl acetate
  • 3,4-dihydroxyphenylethanol
  • L-Lactate Dehydrogenase
  • Phenylethyl Alcohol