Regulacija hepcidina u kroničnoj upali izazvanoj inhalacijskim anesteticima i željezo dekstranom u štakora

master's thesis

• Title (english): Regulation of hepcidin in chronic inflammation induced by inhalation anaesthetics and iron dextran in rats
• Author: Emanuela Adrović
• Mentor: Nada Oršolić (mentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Petar Kružić (član povjerenstva)
• Committee member: Sandra Radić Brkanac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-12-10, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

U radu je istražen učinak inhalacijskih anestetika u nazočnosti željeza na
prooksidacijske/antioksidacijske učinke perifernih tkiva i organa u kroničnoj upali. Cilj rada je
spoznaja kako prekomjerni unos željeza mijenja fiziološke, funkcionalne značajke perifernih
tkiva i kako različiti anestetici mijenjaju metabolizam stanica s obzirom na prijelazne metale
kao inicijatore nastanka reaktivnih vrsta kisika (ROS) i upale kroz regulaciju hepcidina,
transferina i makrofagne polarizacije. Štakori soja Y59 su intraperitonelno (ip) injicirani
otopinom željezo dekstrana u dozi od 50 mg/kg ili su izloženi inhalacijskim anesteticima
sevofluranu (2,4%) i izofluranu (1,3%) te kombinaciji tijekom 28 dana svaki drugi dan.
Rezultati pokazuju da primjena anestetika smanjuje tjelesnu težinu štakora, povećava
oksidacijski stres (OS) u perifernim tkivima vodeći M1 makrofagnoj polarizaciji. Prekomjerni
unos željeza vodi nakupljanju željeza u perifernim tkivima, povećanju OS i upale te povećanju
odnosa IL-12/IL-10 citokina prema M1 makrofagnom fenotipu. Kombinacija sevoflurana i
željeza akumulira željezo u tkivima pokazujući protektivni učinak željeza i M2 fenotip
makrofaga. Kombinacija željezo dekstrana i izoflurana kod štakora vodi hipoksiji, pojačanom
otpuštanju željeza iz makrofaga retikulo-endotelnog sustava te pojačanoj eritropoezi. Razina
hepcidina u jetri regulirana je složenom međureakcijom upale, oksidacijskog stresa, razine
slobodnog željeza, eritropoezom i hipoksijom.

Abstract (english)

The thesis investigates the effect of inhaled anaesthetics in the presence of iron on the
prooxidative/antioxidant effects of peripheral tissues and organs in chronic inflammation. It
intends to understand how excessive iron intake alters physiological, functional characteristics
of peripheral tissues and whether different anaesthetics can alter cell metabolism regarding
transition metals as initiators of reactive oxygen species (ROS) and inflammation through
regulation of hepcidin, transferrin, and macrophage polarization. Y59 rats were injected
intraperitoneally (ip) a solution of iron dextran at a dose of 50 mg/kg or were exposed to inhaled
anaesthetics sevoflurane (2.4%) and isoflurane (1.3%) and the combination for 28 days every
other day. The results show that anaesthetics reduce the rat's body weight and increase
oxidative stress (OS) in peripheral tissues, leading to M1 macrophage polarization. Excessive
iron intake leads to iron accumulation in peripheral tissues, an increase in OS and
inflammation, and an increase in the ratio of IL-12/IL-10 cytokines to the M1 macrophage
phenotype. The combination of sevoflurane and iron accumulates iron in tissues, showing iron's
protective effect and the M2 phenotype of macrophages. The combination of iron dextran and
isoflurane in rats leads to hypoxia, increased iron release from macrophages of the
reticuloendothelial system and increased erythropoiesis. Hepcidin levels in the liver are
regulated by a complex interreaction of inflammation, oxidative stress, free iron levels,
erythropoiesis and hypoxia.

• Keywords: izofluran; sevofluran; homeostaza željeza; upala; oksidacijski stres; makrofagna polarizacija
• Keywords (english): isoflurane; sevoflurane; iron homeostasis; inflammation; oxidative stress; macrophage polarization
• Language: croatian
• URN:NBN: urn:nbn:hr:217:994238
• 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: 2023-12-10
• Created on: 2021-12-15 13:47:30