Učinak alkoholnog ekstrakta propolisa na preživljenje neurona P19 u prisutnosti toksičnih koncentracija iona bakra

master's thesis

• Title (english): Effect of propolis ethanol extract on viability of P19 neurons in the presence of toxic concentrations of copper ions
• Author: Petra Ukić
• Mentor: Maja Jazvinšćak Jembrek (mentor)
• Mentor: Nada Oršolić (mentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Mirta Tkalec (član povjerenstva)
• Committee member: Petar Kružić (član povjerenstva)
• Committee member: Mirjana Kalafatić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015-02-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Oksidacijski stres je jedan od glavnih uzročnika oštećenja neurona. Suvišak iona bakra putem Fentonove reakcije može uzrokovati nakupljanje toksičnih reaktivnih kisikovih vrsta (RKV), posebice hidroksilnog radikala, te izravno pridonijeti nastanku i progresiji raznih neurodegenerativnih bolesti. Propolis kao smjesa spojeva bogata polifenolima ima veliku sposobnost antioksidacijskog djelovanja. Stoga je cilj istraživanja bio utvrditi učinak alkoholnog ekstrakta propolisa na staničnu smrt i oksidacijsko oštećenje izazvano toksičnim koncentracijama bakra u kulturi neurona P19. U ovisnosti o primijenjenoj koncentraciji bakar je smanjio preživljenje neurona P19, dok je toksični učinak alkoholnog ekstrakta propolisa opažen tek pri vrlo visokim koncentracijama. Suprotno očekivanjima, alkoholni ekstrakt propolisa dodatno je smanjio preživljenje neurona P19 istovremeno tretiranih s 1 mM otopinom bakrova sulfata (CuSO4). Neurotoksično djelovanje propolisa uzrokovano je dodatnim stvaranjem RKV-a, kao i pojačanom aktivnošću kaspaza-3/7, te promjenama u ekspresiji gena p53 i c-fos na razini mRNA. Dobiveni rezultati upućuju na prooksidacijsko i proapoptotsko djelovanje alkoholnog ekstrakta propolisa u uvjetima oksidacijskog stresa izazvanog visokim koncentracijama iona bakra. Budući da je dokazana povezanost između suviška bakra i obolijevanja od neurodegenerativnih bolesti, primjena propolisa u ovakvih pacijenata bi mogla imati neželjene posljedice.

Abstract (english)

Oxidative stress is one of the key factors involved in neuronal injury. Excess of copper ions can lead to the accumulation of toxic reactive oxygen species (ROS), especially hydroxyl radicals, via the Fenton chemistry, directly contributing to the development and progression of various neurodegenerative diseases. Propolis, a complex mixture rich in polyphenols, exerts great antioxidative activity. Therefore, the aim of the present study was to investigate the effect of alcoholic extract of propolis on oxidative damage and cell death provoked by toxic levels of copper in the culture of P19 neurons. In a dose-dependent manner, exposure to excess copper for 24 hours reduced survival of P19 neurons, while toxic effects of alcoholic extract of propolis were observed only at very high concentrations. Unexpectedly, alcoholic extract of propolis further decreased survival of P19 neurons exposed to 1 mM copper sulfate (CuSO4). Neurotoxic action of propolis was induced by increased accumulation of ROS and more pronounced caspase-3/7 activity, as well as with changes in the expression of p53 and c-fos mRNA. The obtained results suggest a pro-oxidant and pro-apoptotic potential of alcoholic extract of propolis during neuronal oxidative injury induced by high concentrations of copper ions, and indicate that usage of alcoholic extract of propolis might be contraindicated in patients with copper-related neurodegenerative diseases.

• Keywords: oksidacijski stres; neurotoksičnost; apoptoza; kaspaze-3/7; p53; c-fos
• Keywords (english): oxidative stress; neurotoxicity; apoptosis; caspase-3/7; p53; c-fos
• Language: croatian
• URN:NBN: urn:nbn:hr:217:059817
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-04-24 09:07:32