Učinci nadomjesnog liječenja intravenskim pripravcima željeza na mineralni i antioksidacijski status u bolesnika liječenih hemodijalizom

doctoral thesis

• Title (english): Effects of intravenous iron supplementation treatment on mineral and antioxidative status in hemodialysed patients
• Author: Renat Mujagić
• Mentor: Nada Vrkić (mentor)
• Mentor: Jasna Jurasović (komentor)
• Committee member: Lada Rumora (predsjednik povjerenstva)
• Committee member: Nada Vrkić (član povjerenstva)
• Committee member: Jasna Jurasović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2012-07-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Cilj ovog istraživanja je bio ispitivati povezanost između upale, oksidacijskog stresa,
antioksidacijskog i mineralnog statusa u bolesnika liječenih hemodijalizom s obzirom na primijenjene
načine liječenja. Kliničko značenje sveukupnih međuodnosa između antioksidacijskog sustava obrane,
statusa elemenata u tragovima, upale, oksidacijskog stresa su razmotreni u svrhu odabira primjerenih
postupaka liječenja i hemodijalize.
Stotinu i tri bolesnika liječenih hemodijalizom s potpisanom pisanom privolom (68 muškaraca i 23
žene) su uključeni u kliničko istraživanje. Pedeset i tri bolesnika su intravenski liječeni Ferrlecitom i
eritropoetinom, dok pedeset bolesnika nije primalo Ferrlecit. Trinaest bolesnika nije primalo
antianemike unatrag tri mjeseca. Biokemijski i hematološki pokazatelji su određivani standardnim
harmoniziranim metodama prema smjernicama Hrvatske komore medicinskih biokemičara ili drugim
primjerenim metodama.
Srednjaci koncentracije selena i cinka te aktivnosti pseudokolinesteraze i paraoksonaze su niži od
donje granice referentnog intervala u 103 bolesnika liječenih hemodijalizom. U bolesnika liječenih
Ferrlecitom i eritropoetinom je smanjena aktivnost bakar,cink-superoksid-dismutaze u eritrocitima i
povećana koncentracija feritina u serumu u usporedbi s bolesnicima koji nisu liječeni antianemicima.
Aktivnost serumske superoksid-dismutaze je pozitivno povezana s koncentracijom trovalentnog-netransferinskog
željeza i koncentracijom proteinskih karbonila. Neposredno nakon primjene infuzije
Ferrlecita opažen je porast koncentracije ne-transferinskog željeza i ne-ceruloplazminskog bakra u
serumu s popratnim porastom omjera između dvovalentnog i trovalentnog ne-transferinskog željeza.
Poremećaj metabolizma esencijalnih elemenata u tragovima (nedostatak selena i cinka) s pridruženim
poremećajem antioksidacijskog sustava u eritrocitima (bakar, cink-superoksid-dismutaza) i/ili
antioksidacijskih enzima u plazmi (paraoksonaza) uz pridruženi porast oksidacijskog stresa može
pridonijeti razvoju anemije, upale i pothranjenosti što rezultira aterosklerozom i drugim krvožilnim
komplikacijama u bolesnika liječenih hemodijalizom. Porast aktivnosti serumske superoksiddismutaze
u oksidacijskom stresu predstavlja prilagodbeni odgovor na povećani oksidacijski stres.

Abstract (english)

The aim of this study was to investigate the relationship between inflammation, oxidative stress,
antioxidative and trace elements status in regard to treatment modalities in hemodialysed patients. The
clinical relevance of overall interrelationships between the antioxidative defense system, trace
elements status, inflammation and oxidative stress is considered for optimizing various therapies and
hemodialysis modalities.
A hundred and three hemodialysed patients with signed informed consent (sixty-eight males and
thirty-five females) were included in this clinical trial. Fifty-three patients underwent intravenous
therapy with Ferrlecit and erythropoietin, whereas fifty patients had no Ferrlecit treatment.
Biochemical and hematological parameters were determined by standard harmonized methods
according to the guidelines of the Croatian Chamber of Medical Biochemists or other appropriate
analytical methods.
Mean selenium and zinc plasma concentration and serum pseudocholinesterase and paraoxonase
activity were below the reference range in 103 hemodialysed patients. Patients treated with Ferrlecit
and erythropoietin had a lower copper, zinc-superoxide dismutase activity in erythrocytes and higher
feritin serum concentration. Thereafter, serum superoxide dismutase activity was positively associated
with ferric non-transferrin iron and protein carbonyls level. An increase of non-transferrin iron and
non-ceruloplasmin copper serum concentration accompanied with a concomitant rise of ratio between
ferrous and ferric non-transferrin iron were observed immediately after Ferrlecit infusion.
Essential trace elements metabolism disbalance (selenium and zinc deficiency), with a concomitant
disbalances of the antioxidant system in erythrocytes (copper, zinc-superoxide dismutase) and/or
antioxidant enzymes in plasma (paraoxonase) in addition to occurrence of oxidative stress may
contribute to anemia, inflammation and undernutrition that result with atherosclerosis and other
vascular complication in hemodialysed patients. An increase of serum superoxide dismutase activity in
oxidative stress represents adaptive response to enhanced oxidative stress.

• Keywords: hemodijaliza; antioksidacijski enzimi; elementi u tragovima; upala; oksidacijski stres; željezo; bakar; anemija; eritropoetin; ateroskleroza
• Keywords (english): hemodialyse; antioxidative enzyme; trace elements; inflammation; oxidative stress; iron; copper; anemia; erythropoietin; atherosclerosis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:647343
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-11-17 15:28:29