Učinak kanabidiola na preživljenje stanica SH-SY5Y u prisutnosti toksičnih koncentracija iona bakra

master's thesis

• Title (english): Effect of cannabidiol on viability of SH-SY5Y cells in the presence of toxic concentrations of copper ions
• Author: Marija Perović
• Mentor: Maja Jazvinšćak Jembrek (mentor)
• Mentor: Julija Erhardt (komentor)
• Committee member: Julija Erhardt (predsjednik povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Marija Ivković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-02-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Oksidacijski stres uzrokovan poremećenom regulacijom homeostaze bakra jedan je od važnih čimbenika u patofiziologiji neurodegenerativnih bolesti. Razvoj potencijalnih terapija često uključuje spojeve koji pokazuju antioksidacijska svojstva. Kanabinoidi su skupina lipidnih spojeva s pokazanim antioksidacijskim, protuupalnim i neuroprotektivnim djelovanjem posredstvom endokanabinoidnog sustava. U ovom istraživanju ispitan je učinak kanabidiola na preživljenje stanica SH-SY5Y u fiziološkim uvjetima te u uvjetima oksidacijskog stresa izazvanog visokim koncentracijama bakra. Kanabidiol je, suprotno očekivanjima, djelovao neurotoksično te smanjio preživljenje stanica. Iako nije utjecao na proizvodnju reaktivnih kisikovih vrsta, smanjio je omjer reduciranog i oksidiranog glutationa (GSH/GSSG) kao i aktivnost antioksidacijskog enzima superoksid dismutaze. Također, tretman kanabidiolom je povećao aktivnost izvršnih kaspaza 3 i 7 te kondenzaciju kromatina, kao i otpuštanje laktat dehidrogenaze u stanični medij, što upućuje na staničnu smrt procesima apoptoze i nekroze. Primjena selektivnih inhibitora signalnih puteva povezanih s aktivacijom receptora CB1, kao ni dodatak liganada receptora CB1 nije modificirala učinak kanabidiola na preživljenje stanica, upućujući na to da kanabidiol ne ostvaruje svoje učinke vezivanjem na kanabinoidne receptore.

Abstract (english)

Oxidative stress caused by disturbed regulation of copper homeostasis is one of the important factors in the pathophysiology of neurodegenerative diseases. The development of potential therapies often involves compounds with antioxidant properties. Cannabinoids are lipid compounds with antioxidant, anti-inflammatory and neuroprotective effects achieved through the endocannabinoid system. In this study, the effect of cannabidiol on the survival of SH-SY5Y cells was examined in physiological conditions and in oxidative stress conditions induced by high concentrations of copper. Contrary to expectations, cannabidiol demonstrated neurotoxic effects and reduced cell survival. Although it did not affect the production of reactive oxygen species, it reduced the ratio of reduced and oxidized glutathione (GSH/GSSG), as well as the activity of the antioxidant enzyme superoxide dismutase. Treatment with cannabidiol also increased the activity of executive caspases 3/7 and chromatin condensation, as well as the release of lactate dehydrogenase into the culture medium, which indicates cell death by apoptosis and necrosis. The use of selective inhibitors of signaling pathways associated with CB1 receptor activation, as well as the addition of CB1 receptor ligands did not modify cell survival, suggesting that cannabidiol does not exert its effects via cannabinoid receptors.

• Keywords: oksidacijski stres; kanabinoidi; neurotoksični učinci; receptori CB1; signalni putevi
• Keywords (english): oxidative stress; cannabinoids; CB1 receptors; neurotoxic effects; signaling pathways
• Language: croatian
• URN:NBN: urn:nbn:hr:217:979117
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-02-19
• Created on: 2024-04-22 10:39:28