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Effects of apocynin and hyperbaric oxygenation on ischemia/reperfusion acute kidney injury induced in spontaneously hypertensive rats

dc.contributor.advisorNešović Ostojić, Jelena
dc.contributor.otherIvanov, Milan
dc.contributor.otherLopičić, Srđan
dc.contributor.otherBrkić, Predrag
dc.contributor.otherTodorović, Jasna
dc.creatorKovačević, Sanjin
dc.date.accessioned2022-11-12T14:22:05Z
dc.date.available2022-11-12T14:22:05Z
dc.date.issued2022-06-13
dc.identifier.urihttps://eteze.bg.ac.rs/application/showtheses?thesesId=8815
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:26983/bdef:Content/download
dc.identifier.urihttps://plus.cobiss.net/cobiss/sr/sr/bib/78736393
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/20827
dc.description.abstractIshemijsko/reperfuzijsko oštećenje je čest uzrok akutnog bubrežnog oštećenja (ABO), a hipertenzija može doprineti povećanoj učestalosti i lošijem ishodu ove bolesti. Cilj ove studije je da ispita efekte preventivnog tretmana hiperbaričnom oksigenacijom (HBO) i tretmana apokininom, samostalno ili u kombinaciji na: sistemske i bubrežne hemodinamske parametre, parametre bubrežne funkcije, oksidativni stres, lipidni profil i strukturu bubrežnog tkiva kod spontano hipertenzivnih pacova nakon ishemijsko/reperfuzijskog oštećenja bubrega. Studija je sprovedena na mužjacima spontano hipertenzivnih pacova, koji su nasumično podeljeni u sledeće grupe: lažno operisane pacove (SHAM), pacove sa indukovanim ABO (ABO), grupu sa indukovanim ABO, a kojoj je aplikovan apokinin (ABO+APO), grupu sa HBO tretmanom pre indukcije ABO (ABO+HBO) i grupu sa kombinacijom pretretmana HBO i tretmana apokininom (ABO+APO+HBO). HBO tretman sprovođen je izlaganjem čistom kiseoniku (2.026 bar) dva puta dnevno, dva uzastopna dana, u trajanju od 60 minuta, a 24 časa pre izvođenja ABO. ABO je izvođeno uklanjanjem desnog bubrega i klemovanjem leve bubrežne arterije u trajanju od 45 minuta. Apokinin je aplikovan (40 mg/kg t.m., intravenski) 5 minuta pre reperfuzije. Izazivanje ABO je dovodilo do značajnog pada srednjeg arterijskog pritiska i srčane frekvence, dok je u tretiranim grupama uočen statistički značajan pad ukupnog perifernog vaskularnog otpora. Značajn pad u protoku krvi kroz renalnu arteriju, kao i povećanje vaskularnog otpora u istom krvnom sudu nakon indukcije ABO, poboljšali su se nakon tretmana HBO. Takođe, do jednakog poboljšanja bubrežne hemodinamike dovodio je i tretman apokininom, sa ili bez HBO tretmana. Posmatrajući parametre bubrežne funkcije, ABO je dovodilo do statistički značajnog povećanja koncentracija kreatinina, uree i fosfata u plazmi, kao i smanjenja njihovih urinarnih klirensa. Značajno poboljšanje navedenih parametara, a samim tim i funkcije bubrega uočeno je u svim tretiranim grupama. ABO je dovodilo do promena u lipidnom profilu, sa statistički značajnim povećanjem koncentracija ukupnog i LDL holesterola. Sa druge strane, u poređenju sa ABO grupom, u svim tretiranim grupama uočen je porast HDL holesterola. HBO tretman, primanjen samostalno ili u kombinaciji sa apokininom, dovodio je do smanjenja intenzivne lipidne peroksidacije u plazmi, nastale usled ABO. Takođe, isti tretman, primenjen samostalno, povećavao je aktivnost antioksidativnog enzima glutation – reduktaze, dok je u kombinaciji sa apokininom dovodio do povećane aktivnosti katalaze u eritrocitima. HBO tretman, samostalno ili u kombinaciji sa apokininom, dovodio je do statistički značajnog pada vrednosti KIM – 1 u plazmi. Imunohistohemijska analiza ekspresije 4-HNE, NGAL, i HO-1 u bubrežnom tkivu ukazala je na značajno poboljšanje navedenih parametara u svim tretiranim grupama u odnosu na ABO grupu.sr
dc.description.abstractIschemia/reperfusion injury is common cause of acute kidney injury (AKI), while hypertension might contribute to the increased incidence and worse outcome of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and apocynin treatment on systemic and renal haemodinamics, kidney function, oxidative stress levels, lipid profile and kidney structure in spontaneously hypertensive rats after renal ischemia/reperfusion injury. The study was conducted on male spontaneously hypertensive rats, randomly divided into following groups: sham-operated group (SHAM) AKI control group (AKI), AKI group with apocynin treatment (AKI+APO), group with HBO preconditioning before AKI induction (AKI+HBO) and group with HBO preconditioning before and apocynin treatment after AKI induction (AKI+APO+HBO). HBO preconditioning was performed by exposing to pure oxygen (2.026 bar), twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. Apocynin was applied (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. After AKI induction, mean arterial pressure and hart rate were significantly decreased, while total peripheral vascular resistance was significantly increased in all treated groups. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after HBO preconditioning. Also, apocynin treatment, with or without HBO preconditioning showed improvement on renal hemodynamics. Considering kidney function, AKI significantly increased plasma creatinine, urea and phosphate levels and decreased their urinary clearances. Remarkable improvement, both in plasma concentrations and urinary clarences, in comparison to AKI group was observed in all treated groups. AKI induction caused significant increase in total and LDL cholesterol concentrations in plasma. On the other hand, in all treated group significant increase in HDL cholesterol plasma concentrations was noticed in comparison to AKI group. HBO preconditioning, applied both, solitary or with apocynin decreased intense lipid peroxidation in plasma caused by AKI induction. Also, applied solitary, HBO preconditioning increased glutathione reductase enzyme activity while combined with apocynin, it increased catalase activity in erythrocytes. Increased KIM – 1 plasma levels after AKI induction were significantly decreased after HBO preconditioning, solitary or combined with apocynin. Immunohistochemical analysis of 4-HNE, NGAL, and HO-1 tissue expression in all treated groups showed also significant improvment.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectakutno bubrežno oštećenjesr
dc.subjectacute kidney injuryen
dc.subjecthipertenzijasr
dc.subjecthiperbarična oksigenacijasr
dc.subjectapokininsr
dc.subjecthypertensionen
dc.subjecthyperbaric oxygenen
dc.subjectapocyninen
dc.titleDejstvo apokinina i hiperbarične oksigenacije na ishemijsko/reperfuzijsko akutno bubrežno oštećenje kod spontano hipertenzivnih pacovasr
dc.title.alternativeEffects of apocynin and hyperbaric oxygenation on ischemia/reperfusion acute kidney injury induced in spontaneously hypertensive ratsen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/146971/Disertacija_12741.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/152554/Referat.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_20827


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