DISBIOZA CRIJEVNOG MIKROBIOMA U UPALI PROUZROČENOJ ZDRUŽENIM DJELOVANJEM INHALACIJSKIH ANESTETIKA S TEŠKIM METALIMA U ŠTAKORA

doctoral thesis

• Title (english): GUT MICROBIOME DYSBIOSIS IN INFLAMMATION CAUSED BY THE COMBINED ACTION OF INHALED ANESTHETICS WITH HEAVY METALS IN RATS
• Author: Dyana Odeh
• Mentor: Nada Oršolić (mentor)
• Committee member: Irena Landeka Jurčević (predsjednik povjerenstva)
• Committee member: Sandra Radić Brkanac (član povjerenstva)
• Committee member: Blaženka Kos (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-07-07, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Narušavanje crijevnog mikrobioma snažno je povezano s razvojem patofizioloških bolesti
posredovanim oksidacijskim stresom (OS) u ljudi i životinja. Temeljem toga, cilj rada bio je
dublje razumijevanje odnosa između crijevnog mikrobioma i redoks homeostaze prouzročene
prekomjernim unosom teških metala (TM; Fe i Al) te izlaganja inhalacijskim anesteticima (IA)
kroz praćenje strukturnih i funkcionalnih promjena crijevnog mikrobioma, crijevne barijere,
OS, upale, regulacije hepcidina i feritina, makrofagne polarizacije te funkcionalnih promjena
tkiva i organa. Rezultati ukazuju da subakutna, a posebice kronična primjena IA (sevoflurana i
izoflurana) uz prekomjerni unos TM narušava stanični metabolizam, vodi poremećaju
esencijalnih i nakupljanju TM, povećanju OS, upale, makrofagne polarizacije, imunosne
supresije i disbioze povezane s narušenom brojnošću i raznolikošću crijevnog mikrobioma,
upalom, promjenjenom razinom zonulina, serotonina, enzima mikrobiote i apsorpcije važnih
mikronutrijenata. Razina hepcidina usko je povezana s makrofagnom polarizacijom, OS,
upalom i reorganizacijom oštećenog tkiva, dok je feritin kao upalni biljeg povećan u prisutnosti
metala i/ili IA. Izofluran sam ili u prisutnosti TM izaziva veća oštećenja tkiva od sevoflurana.
Naši podatci naglašavaju molekularno biološku osnovu razumijevanja uloge povezanosti
između IA, TM, crijevnog mikrobioma i makrofagne polarizacije u cilju poduzimanja boljih
terapijskih ili preventivnih mogućnosti zaštite pacijenta od mogućih štetnih posljedica
izazvanih prekomjernim unosom IA, TM i OS.

Abstract (english)

Altered gut microbiome is strongly associated with the development of pathophysiological
diseases mediated by oxidative stress (OS) in humans and animals. Hence, the aim of this thesis
is to get a deeper understanding of the relationship between the gut microbiota and redox
homeostasis caused by excessive intake of heavy metals (HM, Fe and Al) and exposure to
inhalation anesthetics (IA) through monitoring of structural and functional changes of the gut
microbiome, the intestinal barrier, OS, inflammation, regulation of hepcidin and ferritin,
macrophage polarization and functional changes in tissues and organs. The results indicate that
subacute and especially chronic administration of IA (sevoflurane/isoflurane) with excessive
HM intake disrupts cellular metabolism. It further leads to disruption of essential metals and
accumulation of HM, increased OS, inflammation, macrophage polarization, immune
suppression, and dysbiosis associated with altered abundance and diversity of the gut
microbiome, inflammation, altered levels of zonulin, serotonin, microbiota enzymes and
absorption of micronutrients. Hepcidin level is closely related to macrophage polarization, OS,
inflammation, and reorganization of damaged tissue, while ferritin as an inflammatory marker
is increased in the presence of HM and/or IA. Isoflurane alone or in the presence of HM causes
greater tissue damage compared to sevoflurane. Our data emphasize the molecular biological
basis of understanding of the connection between IA, HM, gut microbiome, and macrophage
polarization in order to undertake better therapeutic or preventive options to protect the patient
from possible adverse consequences caused by excessive intake of IA, HM, and OS.

• Keywords: inhalacijski anestetici; antioksidacijski/prooksidacijski učinak; subakutna i kronična upala; makrofagna polarizacija; aluminijev klorid; željezo dekstran; disbioza crijevnog mikrobioma
• Keywords (english): inhaled anesthetic; antioxidant/prooxidant effect; subacute and chronic inflammation; macrophage polarization; aluminum chloride; iron dextran; gut microbiome dysbiosis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:904246
• Promotion: 2023
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-07-07
• Created on: 2023-07-14 12:28:13