аЯрЁБс>ўџ 13ўџџџ0џџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџьЅС5@№ПbjbjЯ2Я2 .­X­Xџџџџџџˆ2222222F....$R FіЖjjjjjEEE]______$ЌRў ƒ-2EEEEEƒ22jjлА999EЌ2j2j]9E]909i22ij^ p- Ъ4|Ь.ё(i]Ц0іi   iFF2222 2iєEE9EEEEEƒƒFFJф#FFJNEUROPROTECTIVE EFFECT OF QUERCETIN AGAINST HYDROGEN PEROXIDE-INDUCED CELL DEATH IN THE CULTURE OF P19 NEURONS Jazvinaak Jembrek Maja, Pevec Tihana, Erhardt Julija, Oraoli Nada Oxidative damage by reactive oxygen species (ROS), secondary intermediates in intracellular signaling, has been implicated in dysfunctions of mammalian brain in numerous diseases and injuries. The aim of this study was to better understand the molecular mechanisms of neurodegeneration induced via oxidative stress and the protective effect of flavonoid quercetin on the neuronal cell death induced by hydrogen peroxide (H2O2) exposure for 24 hours. The effect of quercetin on H2O2-induced injury was investigated in the culture of P19 neurons, differentiated from the P19 mouse embryonal carcinoma cells in the presence of retinoic acid. Complete neuronal maturation of P19 neurons was confirmed by immunofluorescence staining against neuron specific marker beta-III tubulin. As determined by methylthiazolyltetrazolium bromide (MTT) assay, treatment with H2O2 (1.5 mM) significantly decreased the cell viability. In the dose-dependent manner, quercetin reversed the toxic effect of H2O2. Release of lactate dehydrogenase (LDH) from H2O2-damaged cell membranes was also significantly reduced in the presence of quercetin indicating that the P19 neurons were less vulnerable in the presence of quercetin. While H2O2 treatment markedly induced the production of ROS, increase in cell survival in the presence of quercetin was accompanied by a significant decrease in ROS production. Quercetin also decreased the activities of key apoptotic markers caspase-3/7. The obtained results suggest that quercetin, probably due to the interfering with the apoptotic pathway, can act as survival factor in neuronal cells. 4HXzЂор h j ” Р Ь Ю а ў     Y v ‘ В < [ \ ] ^ w x “ ” • – Ÿ ќјєјєј№щхјкЯФкЯМкБкМІБ›“›ˆ|ˆ|ˆqЯeЯeЯh|vghqhRH*mH sH h|vgh!mH sH h|vghUGH*mH sH h|vghUGmH sH hntЂmH sH h|vgh8mH sH h|vghWОmH sH h|vgh–АmH sH h|vgmH sH h|vghše‚mH sH h|vghqhRmH sH h|vgh{r,mH sH h%“ ht8h%“hчhПzАhqhRhI~^$орh j ŒŽєєєєщщщч $dha$gd‰<І $dha$gdЫ_УўŸ І Љ Е Т э ђ 3 … Ѕ Ќ А О Х Ц Я к ѓ і ї џ        4 8 ? ѕэтзЬСЬСЬЖЎСЃ˜Ѓ‚Ѓ‚Ѓwl`l`XM˜M˜h|vghUGmH sH h‰ mH sH h|vgh8H*mH sH h|vgh8mH sH h|vgh›:$mH sH h|vgh%ёmH sH h|vgh*@mH sH h|vghПzАmH sH h|vghotхmH sH hntЂmH sH h|vghБxšmH sH h|vghз{(mH sH h|vghuˆmH sH h|vghcŸmH sH h|vghqhRmH sH hI~^mH sH h|vgh‰<ІmH sH ? 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