Oksidativno-stresni status u krvi i lipoproteinskim frakcijama pacijenata sa hroničnom bolešću bubrega

Abstract

Hronična bolest bubrega (HBB) predstavlja stanje koje se karakteriše brojnim tradicionalnim i netradicionalnim faktorima rizika za razvoj kardiovaskularnih bolesti (KVB). Dislipidemija, oksidativni stres i inflamacija zahvaljujući međusobnim interakcijama predstavljaju faktore koji značajno doprinose patogenezi i progresiji ateroskleroze kod bolesnika sa HBB. Paraoksonaza 1 (PON1) je glavni antioksidativni enzim na HDL česticama, koji svoj antiaterogeni potencijal ostvaruje mehanizmima koji sprečavaju oksidaciju lipoproteina niske gustine (LDL). Prema in vitro studijama u reverznom transportu holesterola mogu učestvovati i membrane eritrocita koje razmenjuju holesterol (RBC-Mh) sa drugim lipoproteinima, kao i hemoglobin koji privremeno uklanja višak holesterola tako što gradi Hb-holesterol kompleks (Hb-h). Brojne studije su pokazale da inflamacija ima važnu ulogu u inicijaciji i progresiji ateroskleroze. Takođe, remodelovanje ekstracelularnog matriksa (ECM) i neadekvatna aktivnost matriks metaloproteinaza (MMP) i tkivnih inhibitora matriks metaloproteinaza (TIMP), kao i galektin-3 doprinose napredovanju hronične bolesti bubrega i razvoju ateroskleroze kod ovih bolesnika. Cilj ove studije je bio ispitivanje parametara dislipidemije, oksidativnog stresa i inflamacije u krvi bolesnika sa HBB, bolesnika na hemodijalizi i zdravih ispitanika. Takođe, ova studija je imala za cilj i ispitivanje uticaja pomenutih faktora rizika na redoks status u glavnim lipoproteinskim frakcijama i na remodelovanje ECM. Cilj je bio i izračunati odgovarajuće skorove dislipidemije, oksidativnog stresa i inflamacije kako bi se procenio sinergistički efekat ovih procesa kao i efekat koji zajedno ostvaruju na oksidativno-stresni status u lipoproteinskim frakcijama kod bolesnika sa različitim stepenom bubrežnog oštećenja. U istraživanju je učestvovalo 77 bolesnika sa različitim stepenom oštećenja funkcije bubrega i 40 zdravih ispitanika. Istraživanje je planirano i sprovedeno prema etičkim principima u skladu sa Helsinškom deklaracijom. Svi parametri oksidativnog stresa, totalni oksidativni status (p<0,01), uznapredovali produkti oksidacije proteina (AOPP) (p<0,01) i tiobarbiturna kiselina reagujuće supstance (p<0,05) su bili značajno viši kod bolesnika sa oštećenom funkcijom bubrega u odnosu na zdrave ispitanike. Vrednosti Hb-h u obe grupe bolesnika su bile niže u odnosu na kontrolnu grupu (p<0,001), dok je s druge strane RBC-Mh bio povišen kod bolesnika na hemodijalizi u poređenju sa kontrolnom grupom (p<0,01). Zdravi ispitanici su imali značajno viši relativni udeo HDL2 subfrakcija u odnosu na bubrežne bolesnike (p<0,05). Koncentracija i aktivnost PON1 u serumu su bile značajno niže u obe grupe bolesnika u odnosu na zdrave ispitanike (p<0,001)...

Chronic kidney disease (CKD) presents condition that is characterized by numerous traditional and non-traditional risk factors for developing cardiovascular disease (CVD). Dyslipidemia, oxidative stress and inflammation due to mutual interaction are factors that significantly contribute to the pathogenesis and progression of atherosclerosis in patients with CKD. Paraoxonase 1 (PON1) is the main antioxidant enzyme on HDL particles, which has antiatherogenic potential by mechanisms that inhibit oxidation of low density lipoprotein particles (LDL). In accordance to in vitro studies reverse cholesterol transport could involve erythrocyte membranes that exchange free cholesterol (RBC-Mc) with other lipoproteins, as well as hemoglobin that temporarily removes excess of cholesterol by building Hbcholesterol complex (Hb-c). Numerous studies have shown that inflammation plays an important role in initiation and progression of atherosclerosis. Also, extracellular matrix (ECM) remodeling and inadequate activity of matrix metalloproteinase (MMP) and tissue matrix metalloproteinase inhibitors (TIMP) as well as galectin-3 also contribute to the progression of chronic kidney disease and atherosclerosis in these patients. The aim of this study was to examine the parameters of dyslipidemia, oxidative stress and inflammation in serum of patients with CKD, dialysis patients and healthy subjects. Also, this study was aimed at examining the influence of the mentioned risk factors on redox status in major lipoprotein fractions and on ECM remodeling. The aim was to calculate summary score of dyslipidemia, oxidative stress and inflammation to evaluate the synergistic effect of these processes as well as the effect on oxidative stress status in lipoprotein fractions in patients with different degrees of renal impairment. The study included 77 patients with different stage of renal function impairment and 40 healthy subjects. The research is planned and implemented according to ethical principles in accordance with the Helsinki Declaration. Healthy subjects had a significantly higher percentage of HDL2 subfractions compared to renal patients (p <0.05). The values of Hb-c in both patients groups were lower than in control group (p <0.001), while values of RBC-Mc were elevated in dialysis patients compared to the control group (p <0.01). All parameters of oxidative stress, total oxidative status (p <0.01), advanced oxidation protein products (AOPP) (p <0.01) and thiobarbituric acid reactive substances (p <0.05) were significantly higher in patients with impaired renal function compared to healthy subjects. Concentration and activity of PON1 in serum were significantly lower in both groups of patients compared to healthy subjects (p <0.001). Arylesterase activity of PON1 was significantly lower in renal patients on HDL2 and HDL3 subclasses (p <0.001). It was found that after hemodialysis there was a significant increase in paraoxonase activity of PON1 (p <0.01), while arylesterase activity of PON1 was lower after dialysis (p <0.01)...