Role of the inhibition of oxidative stress and inflammatory mediators in the neuroprotective effects of hydroxytyrosol in rat brain slices subjected to hypoxia reoxygenation.
The aim of this study was to analyze the mechanism of the neuroprotective effect of hydroxytyrosol (HT) in an experimental model of hypoxia-reoxygenation in rat brain slices. After reoxygenation the increase in lactate dehydrogenase efflux was inhibited by HT in a concentration-dependent manner and dose-dependent inhibition after oral administration to rats for 7 days (1, 5 and 10 mg/kg per day). Maximum inhibition was 57.4% in vitro and 38.7% ex vivo. Hydroxytyrosol reduced oxidative stress parameters: it inhibited lipid peroxidation and increased enzymatic activities related with the glutathione system both in vitro and after oral administration to rats. The increase in prostaglandin E2 and interleukin 1β after reoxygenation were inhibited after incubation of brain slices with HT and after oral administration. The accumulation of nitric oxide in brain slices was reduced in a concentration-dependent manner. In conclusion, HT exerts a neuroprotective effect in a model of hypoxia-reoxygenation in rat brain slices, both in vitro and after 7 days of oral administration to rats. HT exerts an antioxidant activity and lowered some inflammatory markers in this model.
Laboratorio de Investigaciones Antitrombóticas e Isquemia Tisular (LIAIT), Department of Pharmacology and Therapeutics.
Susana
S
Cabrerizo
José Pedro
JP
De La Cruz
Juan Antonio
JA
López-Villodres
Javier
J
Muñoz-Marín
Ana
A
Guerrero
José Julio
JJ
Reyes
María Teresa
MT
Labajos
José Antonio
JA
González-Correa
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D059808:Polyphenols; D017392:Thiobarbituric Acid Reactive Substances; C005975:3,4-dihydroxyphenylethanol; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D015232:Dinoprostone; D010626:Phenylethyl Alcohol
GSH; GSHpx; GSHtf; GSSG; HT; Hydroxytyrosol; Hypoxia-reoxygenation; IL-1β; Inflammation; LDH; MDA; NO(-)(2) + NO(-)(3); Neuroprotection; Oxidative stress; PGE(2); TBARS; glutathione peroxidase; glutathione transferase; hydroxytyrosol; interleukin 1β; lactate dehydrogenase; malondialdehyde; nitrites + nitrates; oxidized glutathione; prostaglandin E(2); reduced glutathione; thiobarbituric acid reactive substances