Neurodegenerativne promjene u mozgu štakora izazvane sevofluranom i željezo-dekstranom

master's thesis

• Title (english): Neurodegenerative changes in the rat brain induced by sevoflurane and iron-dextran
• Author: Biljana Pamučar
• Mentor: Nada Oršolić (mentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Renata Matoničkin Kepčija (član povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Duje Lisičić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018-01-30, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Inhalacijski anestetici su lako hlapljive tekućine, a služe za uvođenje ili održavanje anestezije pri operativnim zahvatima nepredvidljivog trajanja. U ovom radu proučavan je utjecaj sevoflurana, samog ili združenog s željezo-dekstranom, na nastanak i razvoj neurodegenerativnih promjena na tkivu mozga štakora. Neurodegeneracija je mjerena: (i) promjenama oksidacijskog statusa mjerenjem razine malondialdehida (MDA), glutationa (GSH), te enzimatske aktivnosti katalaze (CAT) i superoksid dismutaze (SOD); (ii) (anti)genotoksičnog odgovora u limfocitima štakora, pokazujući razinu oštećenja DNA; (iii) procjenom razine neuroupale prema relativnoj težini mozga u odnosu na zdravu kontrolu; (iv) procjenom toksičnog učinka na hematološke i biokemijske odrednice u krvi, te osmotsku fragilnost eritrocita. Rezultati pokazuju da željezo-dekstran uzrokuje značajnu neuroupalu, te povećanu razinu oksidacijskog stresa: povećava razinu MDA, mijenja aktivnosti antioksidativnih enzima (SOD, CAT) i snižava GSH. Sevofluran u kombinaciji sa Fe-dekstranom pokazuje izraženi gubitak moždanih stanica i prividno niske razine MDA te antioksidansa, kao i značajne toksične učinke na krvne odrednice. Comet test pokazuje najveća oštećenja DNA limfocita pri izlaganju sevofluranu združenim sa željezo-dekstranom. Temeljem rezultata može se zaključiti kako jaka neuroupala i pojava lipidne peroksidacije u mozgu životinja obrađenih Fe-dekstranom ukazuju na neurotoksičnost, dok kombinacija sa sevofluranom uzrokuje najteža oštećenja mozga i trajno narušava homeostazu organizma.

Abstract (english)

Inhalation anaesthetics, such as sevoflurane, are commonly used in modern medicine. They are volatile gases that easily diffuse through cell membranes, used as the introduction to anaesthesia or for maintaining it in procedures of unpredictable duration. Aim of this study was to study the effects of sevoflurane, alone or in combination with Fe-dextran, on development of neurodegenerative changes in the rat brain tissue. Neurodegeneration was evaluated by: (i) (anti)oxidative status of brain tissue, by measuring the malondialdehyde (MDA) and glutathione (GSH) concentrations, catalase (CAT) and superoxide dismutase (SOD) enzymatic activities; (ii) (anti)genotoxic response in rat lymphocytes, indicating extent of DNA damage; (iii) neuroinflammation, evaluated with relative brain weight compared to healthy control; (iv) toxic effects on haematological and biochemical blood parameters, and osmotic fragility of erythrocytes. Results show that Fe-dextran causes neuroinflammation and oxidative stress: it increases MDA concentration, SOD and CAT activity and decreases GSH. Sevoflurane combined with Fe-dextran causes extensive neuroapoptosis and seemingly low MDA and antioxidant concentrations, with the highest blood toxicity and DNA damage. In summary, severe neuroinflammation and lipid peroxidation in brain of Fe-dextran treated animals indicate neurotoxicity, whereas combination with sevoflurane causes severe neurodegeneration and permanently affects whole body homeostasis.

• Keywords: inhalacijski anestetici; sevofluran; željezo; neurotoksičnost; oksidacijski stres
• Keywords (english): inhalation anaesthetics; sevoflurane; iron; neurotoxicity; oxidative stress
• Language: croatian
• URN:NBN: urn:nbn:hr:217:201945
• 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: 2020-01-30
• Created on: 2018-03-15 11:30:11