Učinak antiepileptika valproata na antioksidacijski sustav u neciljnim stanicama i tkivima

master's thesis

• Title (english): Antiepileptic valproate effect on antioxidative defence system in non-target cells and tissues
• Author: Elena Marić
• Mentor: Domagoj Đikić (mentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Committee member: Davor Zanella (član povjerenstva)
• Committee member: Željka Vidaković-Cifrek (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018-11-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Cilj rada bio je istražiti kako tretman antiepileptikom valproatom utječe na razine antioksidacijskih
enzima in vitro i in vivo u jetri i bubregu miševa (C57Bl6) te na staničnim modelima CHO, PK15
i HEPG2 te usporediti rezultate. Nakon tretmana valproatom in vivo i in vitro, u homogenatima
bubrega i jetre miševa i u stanicama iz stanične kulture, izmjerena je lipidna peroksidacija odnosno
razina malonilaldehida, koncentracija ukupnog glutationa te aktivnost antioksidacijskih enzima
superoksid dismutaze i katalaze. U jetri mužjaka i ženki valproat uzrokuje smanjenu koncentraciju
malonilaldehida (MDA) odnosno manju lipidnu peroksidaciju u odnosu na pripadajuće kontrolne
skupine. Slično je zabilježeno i u staničnom modelu, pri čemu jetrene stanice HEPG2, reagiraju sa
smanjenom koncentracijom lipidne peroksidacije nakon 24 satnog tretmana s koncentracijama od
10, 70 i 100 mM valproata u staničnoj kulturi. Stanični model bubrega u kulturi, s obzirom na
trend promjene antioksidacijskih parametara uglavnom slijedi slične promjene kao i u in vivo te se
zaključno može reći da je PK stanični model oksidacijskog stresa uzrokovanog valproatom dobra
zamjena za in vivo mišji model. Za razliku od PK15 stanica, HEPG2 stanice nisu pokazale slične
promjene antioksidativnog sustava kao i jetra tretiranih miševa.

Abstract (english)

The aim of the study was to investigate how the antiepileptic valproate treatment affects the levels
of antioxidative enzymes in vitro and in vivo in the liver and kidney of the mice (C57Bl6) and on
the CHO, PK15 and HEPG2 cellular models and compare the results. After valproate treatment in
vivo and, lipid peroxidation, ie malonilaldehyde levels, total glutathione concentration and
antioxidant enzyme activity of superoxide dismutase and catalase were measured. In the liver of
males and females, valproate caused a decrease in MDA or lower lipid peroxidation relative to the
associated control group. Similarly, in the cell model, and the HEPG2 dairy cells reacted with
reduced lipid peroxidation concentrations after 24 hours of treatment at concentrations of 10, 70
and 100 mM valproate in cell culture. The cellular model of the kidney in culture, mainly followed
the similar changes as in vivo and it can be concluded that the PK cellular model of oxidative stress
caused by valproate is a good replacement for an in vivo mouse model. Unlike PK15 cells, HEPG2
cells did not show similar changes in the antioxidative system as liver-treated mice.

• Keywords: valproat; valproična kiselina; oksidativni stres; lipidna peroksidacija; superoksid dismutaza; katalaza; glutation
• Keywords (english): valproate; valproic acid; oxidative stress; lipid peroxidation; superoxide dismutase; catalase; glutathione
• Language: croatian
• URN:NBN: urn:nbn:hr:217:988982
• 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; Embargo expiration date: 2020-11-27
• Created on: 2019-03-28 11:29:24