Title Detoksikacija jetre zeolitom PMAO2 nakon intoksikacije aluminijevim kloridom
Title (english) Liver detoxification with PMAO2 zeolite after aluminum chloride intoxication
Author Darko Gumbarević
Mentor Sandra Kraljević Pavelić (mentor)
Committee member Elitza Petkova Markova - Car (predsjednik povjerenstva)
Committee member Ivan Gudelj (član povjerenstva)
Committee member Ljiljana Bedrica (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2022-04-28, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology
Universal decimal classification (UDC ) 577 - Biochemistry. Molecular biology. Biophysics
Abstract Aluminij je metal 13. skupine periodnog sustava elementa te nema fiziološku ulogu u
organizmu. Povezuje se s nizom bolesti poput: Alzheimerove bolesti, Parkinsonove
bolesti, Downovog sindroma, autizma itd. Sve veće globalne klimatske promjene
dovele su do povišenja razine aluminija u okolišu i ulazak u biota. Trenutno ne postoji
metoda za njegovo uklanjanje iz okoliša ili za detoksikaciju živih organizama pa tako i
čovjeka. Postojeća pak terapija protiv trovanja aluminijevim solima je desferioksamin.
Kako isti ima veliki broj nuspojava, zadnjih godina se istražuje mogućnost korištenja
alternativnih načina detoksikacije aluminija u živim organizmima, primjerice
korištenjem zeolita klinoptilolita koji su poznati ionski izmjenjivači, adsorbensi te
otpuštaju ortosilicijevu kiselinu što je u kontekstu detoksikacije aluminija također
izuzetno važno svojstvo. U ovom doktoratu istražena su fizikalno-kemijska svojstva
prirodnih zeolitnih klinoptilolitnih materijala, tribomehanički aktiviranog klinoptilolita
TMAZ, dvostruko tribomehanički aktiviranog zeolita PMA i dvostruko tribomehanički
aktiviranog oksigeniranog zeolita PMAO2 te je kao kontrolni spoj korišten sintetski
zeolit A. Fizikalno-kemijska svojstva zeolitnih materijala bitna su za objašnjenje
interakcije s ionima i biomolekulama u biološkim sustavima te su u ovom doktoratu
provedeni eksperimenti infracrvene spektroskopije s Fourierovom transformacijom,
određivanje zeta potencijala i pH zeolitnih suspenzija u vodi i modelnim otopinama
crijeva i želuca, in vitro kapacitet vezanja teških metala za zeolitne materijale,
određivanje veličine čestica dinamičkim raspršenjem svjetlosti, analiza sastava i
izgleda površine materijala metodom XPS/EDS. Svi su istraženi zeolitni klinoptilolitni
materijali pokazali značajan kapacitet vezanja kationa olova u modelnoj otopini
želuca i crijeva te arsena, kroma i nikla u modelnoj otopini crijeva. Nadalje, svi su
zeolitni klinoptololitni materijali pokazali detoksikacijska svojstva na aluminij in vivo
na modelu intoksiciranih štakora subkroničnim dozama aluminijevog klorida.
Mehanizam djelovanja ovog svojstva istražen je za PMAO2 analizom jetre životinja
metodom DNA mikročipova koja je pokazala aktivaciju gena Sfrp1,Cry1, Rassf8 i
supresiju gena Nr1d2 u tkivu jetre koji su uključeni u mehanizme detoksikacije. Ovi
rezultati govore u prilog primjeni zeolita klinoptilolita u medicinske svrhe
Abstract (english) Aluminum is a metal in the 13th group of the periodic table of elements and has no
physiological role in the body. It has been linked to a number of diseases such as
Alzheimer's, Parkinson's, Down syndrome, autism, etc. Increasing global climate
change has led to an increase in the concentration of aluminum in the environment
and its entry into the biota. Currently, there is no method to remove it from the
environment, or to detoxify living organisms, including humans. The existing therapy
for aluminum salt poisoning is desferrioxamine. As it has large number of side
effects, in recent years possibility of using alternative ways of detoxification of
aluminum in living organisms has been investigated, for example by using
clinoptilolite zeolites which are known ion exchangers, adsorbents and orthosilicic
acid realising compounds which is also extremely important in the context of
aluminum detoxification. Therefore, the physicochemical properties of natural zeolite
clinoptilolite materials tribomechanically activated clinoptilolite TMAZ, double
tribomechanically activated zeolite PMA and double tribomechanically activated
oxygenated zeolite PMAO2 were investigated in this doctorate and synthetic zeolite
A was used as a control compound. Physicochemical properties of zeolite materials
are important for explaining interactions with ions and biomolecules in biological
systems and in this doctorate were performed experiments with Fourier transformed
infrared spectroscopy, determination of zeta potential, pH of zeolite suspensions in
model solutions of intestine and stomach as well as in water, in vitro binding capacity
of heavy metals, determination of particle size by dynamic light scattering and
surface analysis of the materials by XPS / EDS. All investigated clinoptilolite
materials showed a significant binding capacity of lead cations in model solution of
stomach and intestines and arsen, chromium and nickel in the model solution of the
intestines. Furthermore, all zeolite clinoptilolite materials showed detoxifying
properties on aluminum in vivo in a model of intoxicated rats by subchronic doses of
aluminum chloride. The mechanism of action of this property was investigated for
PMAO2 analysis of animal liver by DNA microchip method which showed activation
of Sfrp1, Cry1, Rassf8 genes and supression of Nr1d2 genes in liver tissue involved
in detoxification mechanisms. These results support the use of clinoptilolite zeolite for
medical purposes.
Keywords
aluminij
ortosilicijeva kiselina
zeolit klinoptilolit
fizikalno kemijska svojstva
DNA mikročipovi
detoksikacija jetre zeolitom PMAO2
Keywords (english)
aluminum
orthosilicic acid
zeolite-clinoptilolite
physicochemical properties
DNA microarrays
detoxification of liver with PMAO2 zeolite
Language croatian
URN:NBN urn:nbn:hr:193:959295
Promotion 2023
Study programme Title: Medicinal chemistry Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini (doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2023-02-08 07:55:34