Uloga mitohondrija u patofiziologiji ishemijsko-reperfuzijske ozljede

master's thesis

• Title (english): The role of mitochondria in pathophysiology of ischemia-reperfusion injury
• Author: Dora Meštrović
• Mentor: Filip Sedlić (mentor)
• Committee member: Nino Sinčić (predsjednik povjerenstva)
• Committee member: Borislav Belev (član povjerenstva)
• Committee member: Filip Sedlić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pathophysiology); Zagreb
• Defense date and country: 2023-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathophysiology

Abstract

Ishemijsko-reperfuzijska (IR) ozljeda predstavlja jedan od najčešćih uzroka stanične ozljede. Ishemijske bolesti srca i mozga ostaju, unatoč značajnom razvoju farmakološkog i kirurškog liječenja te prevencije tih bolesti, i dalje među glavnim uzrocima morbiditeta i mortaliteta u razvijenim zemljama. Novija istraživanja ukazuju na to da mitohondriji, kao stanične organele zadužene za proizvodnju ATP-a, regulaciju unutarstanične koncentracije Ca2+ i važni izvori reaktivnih kisikovih spojeva (engl. reactive oxygen species, ROS), imaju važnu ulogu u nastanku IR ozljede.

U ovome diplomskom radu predstavit ću brojne mehanizme putem kojih mitohondriji mogu sudjelovati u patogenezi IR ozljede, uključujući sintezu ROS-a, oslobađanje mitohondrijskog Ca2+ i promjene dinamike fisije i fuzije. Nakon predstavljanja pojedinih mehanizma koji dovode do IR ozljede predstavit ću potencijalnu farmakološku terapiju vezanu uz iste. Također ću iznijeti neke od preventivnih farmakoloških metoda koje bi mogle značajno smanjiti opseg te ozljede. Uz to, spomenut ću neke od studija na životinjama i značajnija klinička istraživanja.

U konačnici, raspravit ću o prednostima i nedostatcima farmakološke terapije usmjerene prema mitohondrijima te ću opisati predstojeće izazove koji moraju biti prevladani prije šire upotrebe ove terapije.

Abstract (english)

Ischemia-reperfusion (IR) injury is one of the most common causes of cellular injury. Ischemic diseases of the heart and the brain have remained, despite significant progress achieved in the pharmacological and surgical treatment and, a major cause of morbidity and mortality in developed countries. Recent studies showed that mitochondria, as an organelles responsible for production of ATP, intracellular Ca2+ regulation and rective oxygen species (ROS) production, play a key role in the IR injury.

In this thesis, I will focus on the various mechanisms through which mitochondria participate in the pathogenesis of IR injury, including ROS synthesis, release of mitochondrial calcium and changes in the fusion-fission dynamics. After presenting mechanisms that lead to IR injury, I will present potential pharmacological treatments aimed at these mechanisms. I will also discuss certain pharmacological methods of prevention which may considerably reduce the extent of the injury. In addition, important animal and clinical studies will be discussed.

Finally, advantages and disadvantages of pharmacological therapy targeting the mitochondria will be discussed, as well as some of the future challenges that must be overcome to enable wider use of this therapy.

• Keywords: ishemijsko-reperfuzijska ozljeda; mitohondriji; terapija
• Keywords (english): ischemia-reperfusion injury; mitochondria; therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:405925
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-26 10:43:08