Uloga angiotenzina II i reaktivnih vrsta kiseonika tokom razvoja akutne bubrežne insuficijencije u eksperimentalnoj hipertenziji

Acute renal failure (ARF) is defined as a sudden loss of renal function. It’s multifactorially caused, but the mechanism of pathogenesis and developement of this disease is still uncomplitely defined. ARF is characterized by sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. ARF frequently occurres with hospitalized patients. The frequency of its occurrence in the intensive care units moves up to 30%. Associated with other diseases, such as hypertension, it causes high rate mortality. Recent studies show that hypertension and oxidative stress have an important role in the renal disease progression. This fact directed the focus of our study towards the influence of these two pathogenetic factors in development and progression of ARF. The system rennin angiotensin aldosterone (RAAS) has a great role in blood pressure control and kidney homeostatic mechanisms. It mostly regulates the renal hemodynamic, but considering the fact that the intrarenal vasoconstriction is one of the major mechanisms of ARF development, it obviously influences the pathogenetic mechanisms in the development of this disorders. Oxidative stress is defined as a disbalance between the production of reactive oxygen species (ROS) and an ability of biological system to remove or fix the damage made due to production of these molecules. Reactive oxygen species are highly reactive due to presence of unpaired electrons and consequently lead to damage of DNA, RNA and some other ageing related proteins. There is evidence that the oxidative stress has a great influence in the progression of numerous diseases, such as Alzheimer’s, Parkinson’s, as well as some cardiovascular disorders. Furthermore, during the ischemia/reperfusion injuries of organs and tissues, there is increased reactive oxygen species molecule production. Thus, the ischemic type of ARF is characterized by a high concentration of these molecules which contribute to the development of this devastating illnes...Akutna bubrežna insuficijencija (ABI) se definiše kao nagli gubitak bubrežne funkcije. Uzroci nastanka ABI su mnogobrojni, a mehanizmi razvoja još uvek nedovoljno jasni. Karakterišu je iznenadna pojava, brzi tok, neizvesna i često loša prognoza krajnjeg ishoda bolesti. ABI je česta pojava kod hospitalizovanih pacijenata, a učestalost njenog nastanka na odeljenjima intenzivne nege se kreće do 30%. Udružena sa drugim oboljenjima, poput hipertenzije, uzrokuje visok stepen mortaliteta. Savremena istraživanja pokazuju da hipertenzija i oksidativni stres imaju važnu ulogu u progresiji bubrežnih oboljenja, što je usmerilo i stavilo akcenat naših istraživanja na uloge ova dva patogenetska faktora u nastanku i progresiji ABI. Sistem renin angiotenzin aldosteron (RAAS) ima značajnu ulogu u održanju krvnog pritiska i homeostatskih mehanizama bubrega. On u velikoj meri reguliše bubrežnu hemodinamiku i vaskularnu reaktivnost, a kako je intrarenalna vazokonstrikcija jedan od glavnih mehanizama razvoja ABI, očita je njegova uloga u patogenetskim mehanizmima nastanka ove bolesti. Oksidativni stres predstavlja disbalans između produkcije reaktivnih vrsta kiseonika (RVK) i sposobnosti biološkog sistema da ih uklanja ili da reparira oštećenja nastala produkcijom ovih molekula. Reaktivne vrste kiseonika su izuzetno reaktivne supstance usled postojanja nesparenih elektrona, i kao takve mogu da uzrokuju oštećenja na DNK, RNK, kao i nekim proteinima koji imaju ulogu u procesu starenja. Pokazano je da oksidativni stres ima veliku ulogu u razvoju mnogih oboljenja, kao što su Alchajmerova i Parkinsonova bolest, i neki kardiovaskularni poremećaji. Takodje je dokazano da, prilikom ishemičnih povreda organa i tkiva, nakon hipoksije, a tokom reperfuzije, dolazi do povećane produkcije molekula RVK. Iz pomenutih razloga, sasvim je izvesno da u ishemičnoj formi ABI povećana koncentracija ovih molekula, doprinosi nastanku i razvoju ovog teškog oboljenja..

The role of angiotensin II and reactive oxygen species during the acute renal failure development in experimental hypertension

Akutna bubrežna insuficijencija (ABI) se definiše kao nagli gubitak bubrežne funkcije. Uzroci nastanka ABI su mnogobrojni, a mehanizmi razvoja još uvek nedovoljno jasni. Karakterišu je iznenadna pojava, brzi tok, neizvesna i često loša prognoza krajnjeg ishoda bolesti. ABI je česta pojava kod hospitalizovanih pacijenata, a učestalost njenog nastanka na odeljenjima intenzivne nege se kreće do 30%. Udružena sa drugim oboljenjima, poput hipertenzije, uzrokuje visok stepen mortaliteta. Savremena istraživanja pokazuju da hipertenzija i oksidativni stres imaju važnu ulogu u progresiji bubrežnih oboljenja, što je usmerilo i stavilo akcenat naših istraživanja na uloge ova dva patogenetska faktora u nastanku i progresiji ABI. Sistem renin angiotenzin aldosteron (RAAS) ima značajnu ulogu u održanju krvnog pritiska i homeostatskih mehanizama bubrega. On u velikoj meri reguliše bubrežnu hemodinamiku i vaskularnu reaktivnost, a kako je intrarenalna vazokonstrikcija jedan od glavnih mehanizama razvoja ABI, očita je njegova uloga u patogenetskim mehanizmima nastanka ove bolesti. Oksidativni stres predstavlja disbalans između produkcije reaktivnih vrsta kiseonika (RVK) i sposobnosti biološkog sistema da ih uklanja ili da reparira oštećenja nastala produkcijom ovih molekula. Reaktivne vrste kiseonika su izuzetno reaktivne supstance usled postojanja nesparenih elektrona, i kao takve mogu da uzrokuju oštećenja na DNK, RNK, kao i nekim proteinima koji imaju ulogu u procesu starenja. Pokazano je da oksidativni stres ima veliku ulogu u razvoju mnogih oboljenja, kao što su Alchajmerova i Parkinsonova bolest, i neki kardiovaskularni poremećaji. Takodje je dokazano da, prilikom ishemičnih povreda organa i tkiva, nakon hipoksije, a tokom reperfuzije, dolazi do povećane produkcije molekula RVK. Iz pomenutih razloga, sasvim je izvesno da u ishemičnoj formi ABI povećana koncentracija ovih molekula, doprinosi nastanku i razvoju ovog teškog oboljenja...Acute renal failure (ARF) is defined as a sudden loss of renal function. It’s multifactorially caused, but the mechanism of pathogenesis and developement of this disease is still uncomplitely defined. ARF is characterized by sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. ARF frequently occurres with hospitalized patients. The frequency of its occurrence in the intensive care units moves up to 30%. Associated with other diseases, such as hypertension, it causes high rate mortality. Recent studies show that hypertension and oxidative stress have an important role in the renal disease progression. This fact directed the focus of our study towards the influence of these two pathogenetic factors in development and progression of ARF. The system rennin angiotensin aldosterone (RAAS) has a great role in blood pressure control and kidney homeostatic mechanisms. It mostly regulates the renal hemodynamic, but considering the fact that the intrarenal vasoconstriction is one of the major mechanisms of ARF development, it obviously influences the pathogenetic mechanisms in the development of this disorders. Oxidative stress is defined as a disbalance between the production of reactive oxygen species (ROS) and an ability of biological system to remove or fix the damage made due to production of these molecules. Reactive oxygen species are highly reactive due to presence of unpaired electrons and consequently lead to damage of DNA, RNA and some other ageing related proteins. There is evidence that the oxidative stress has a great influence in the progression of numerous diseases, such as Alzheimer’s, Parkinson’s, as well as some cardiovascular disorders. Furthermore, during the ischemia/reperfusion injuries of organs and tissues, there is increased reactive oxygen species molecule production. Thus, the ischemic type of ARF is characterized by a high concentration of these molecules which contribute to the development of this devastating illnes..

Redescription of the soft-shell turtle Rafetus bohemicus (Testudines, Trionychidae) from the Early Miocene of Czechia

The taxonomy of the soft-shell turtle Rafetus bohemicus (Liebus, 1930), family Trionychidae, subfamily Trionychinae, is revised based on new and previously mentioned material (including the type material) from the Early Miocene (Burdigalian, MN 3) sites of the Most Basin, Czechia. Given that the diagnosis was so far based only on plastral elements, here we focused on the cranial material and combined our study with previously published data on postcranial elements. 3D models of the skulls derived from CT scans allow us to provide the first complete skull description of R. bohemicus, including several new cranial diagnostic characters of the species. Our results not only enable the distinction of the trionychid genera Trionyx and Rafetus, both recorded from Central Europe during the Early Miocene, but further allow us to provide an emended diagnosis for R. bohemicus. We confirm the conclusions of a previous study according to which Trionyx pontanus, T. preschenensis, T. aspidiformis, and T. elongatus are nomina dubia. R. bohemicus from Břešt'any (MN 3) represents the oldest record of this genus in Europe as well as the oldest occurrence of the genus

Optimization of the extraction of antioxidants from stinging nettle leaf using response surface methodology

The aim of this study was to optimize the parameters for the extraction of total flavonoids from stinging nettle leaf. Comparison of the effects of different solvents on total flavonoid content showed that, regardless of extraction time, aqueous methanolicextracts had higher total flavonoid content than did aqueous ethanolic extracts. So, full factorial design and response surface methodology (RSM) were em-ployed to estimate the effects of methanol content (50, 75and 100%) and extraction time (30, 60and 90 min) on the total flavonoid content and antioxidant capacities of the extracts. RSM analysis showed that methanol content in the solvent influenced significantly total flavonoid content and FRAP (ferric-reducing antioxidant power) antioxidant capacity, while extraction time had no significant effect on either of these responses. Extraction parameters for maximal total flavonoid content were estimated to be 69% aqueous methanol and 67 min, and 65% aqueous methanol and 83 min for maximal FRAPantioxidantcapacity. DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity was not significantly affected by extraction time or methanol percentage in the solvent

Uticaj hronične promene vrednosti hematokrita na krvni pritisak i glomerulsku filtraciju kod pacova sa urođenom hipertenzijom

Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR). Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite - lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.Brojna ispitivanja izvedena na životinjama i ljudima su ukazala da je povećanje viskoznosti krvi u direktnoj vezi sa hipertenzijom. Cilj naše studije je bio da se istraži uticaj promene vrednosti hematokrita (Hct) na krvni pritisak i funkciju bubrega u urođenoj hipertenziji. U tom cilju, istraživan je uticaj hroničnog povećanja ili smanjenja vrednosti Hct na hemodinamske parametre, vaskularnu reaktivnost, glomerulsku filtraciju i krivu bubrežne funkcije kod pacova sa urođenom hipertenzijom (SHR). Rezultati naše studije su ukazali da hronično povećanje vrednosti Hct dovodi do povećanja arterijskog krvnog pritiska (AKP) i perifernog vaskularnog otpora (PVO) kod SHR . Nasuprot tome, hronično smanjenje vrednosti Hct dovodi do smanjenja AKP i PVO, praćenih povećanjem minutnog volumena srca. Obe promene vrednosti Hct dovode do smanjenja vaskularne reaktivnosti. Hronično smanjenje vrednosti Hct izaziva nastanak akutne bubrežne insuficijencije. Ekskrecija natrijuma je pomerena ka većim vrednostima krvnog pritiska kod pacova sa povećanim vrednostima Hct, a ka nižim kod pacova sa sniženim vrednostima Hct. Hronično povećanje vrednosti Hct dovodi do razvoja maligne hipertenzije kod SHR. Potrebne su dalje studije da bi se utvrdio tačan stepen i priroda oštećenja bubrega nakon hronične promene vrednosti Hct

Uticaj blokade receptora tip 1 za angotenzin II udružene sa uklanjanjem superoksidnog anjona na postishemični bubreg kod pacova sa urođenom hipertenzijom

Ischemic acute kidney injury is characterized by renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and overproduction of angiotensin II and reactive oxygen species. Considering this complexity, the aim of our study was to investigate the effects of angiotensin II type-1 receptor blocker - Losartan and superoxide anion scavenger - Tempol, in a combined treatment on acute kidney injury in postischemic hypertensive rats. The experiment was performed in anesthetized, adult male spontaneously hypertensive rats. The right kidney was removed and the left renal artery was occluded for 40 minutes. Experimental groups received combined treatment (Losartan + Tempol) or saline in the femoral vein 5 minutes before, during and 175 minutes after clamp removal. Hemodynamics and biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. Histological examination was performed by optical microscopy. Combined treatment improves renal haemodynamics parameters which were exacerbated due to acute kidney injury. Acute kidney injury significantly decreased creatinine and urea clearance and increased lipid peroxidation in the plasma. Treatment with Losartan and Tempol induced a significant increase of creatinine and urea clearance. Lipid peroxidation in the plasma decreased and glutathione peroxidase enzyme activity in the erythrocytes increased after Losartan + Tempol treatment. This combined treatment reduced cortico-medullary necrosis and tubular dilatation in the kidney. Our results indicate that synergism of Losartan and Tempol treatment could have beneficial effects on blood pressure and kidney function, during postischemic acute kidney injury development in experimental hypertension.Glavne karakteristike ishemične akutne bubrežne slabosti su: renalna vazokonstrikcija, pad glomerulske filtracije, tubularna opstrukcija, vraćanje glomerulskog filtrata u intersticijum tubula i prekomerna produkcija angiotenzina II i reaktivnih vrsta kiseonika. Uzimajući u obzir kompleksnost ovog poremećaja, cilj ove studije je bio da istraži efekte kombinovanog tretmana blokatora angiotenzin II receptora tip 1 - Losartana i sakupljača superoksidnog anjona - Tempola u modelu ishemične bubrežne slabosti kod hipertenzivnih pacova. Eksperiment je urađen na odraslim anesteziranim mužjacima hipertenzivnih pacova. Desni bubreg je uklonjen, dok je na levoj renalnoj arteriji urađena okluzija u trajanju od 40 minuta. Eksperimentalne grupe su primile kombinovani tretman (Losartan+Tempol) ili fiziološki rastvor u femoralnu venu, 5 minuta pre i 175 minuta nakon uklanjanja kleme sa renalne arterije. Hemodinamski i biohemijski parametri su izmereni, a uzorci bubrega uzimani su 24 časa nakon reperfuzije. Histološka ispitivanja su rađena pomoću svetlosnog mikroskopa. Kombinovani tretman poboljšava renalnu hemodinamiku, poremećenu usled ishemične akutne bubrežne slabosti. U ovom modelu bubrežne slabosti dolazi do pada klirensa kreatinina i uree, i povećanja lipidne peroksidacije u plazmi.Tretman Losartanom i Tempolom dovodi do značajnog povećanja klirensa kreatinina i uree. Lipidna peroksidacija je smanjena, a aktivnost glutation peroksidaze u eritrocitima je povećana nakon kombinovanog tretmana sa Losartanom i Tempolom. Takođe, ovakav kombinovan tretman smanjuje kortiko-medularnu nekrozu i tubularnu dilataciju u bubregu. Naši rezultati ukazuju na to da sinergizam Losartana i Tempola može imati povoljan efekat na krvni pritisak i bubrežnu funkciju tokom razvoja postishemične akutne bubrežne slabosti u eksperimentalnoj hipertenziji

Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats

Limited numbers of studies include research of microvibration therapy in experimental models. We examined effects of chronic vibroacustic-microvibration treatment on haemodynamics and anti-oxidative defense in experimental hypertension. Study was performed on chronically treated hypertensive and normotensive Wistar rats. Mean arterial pressure (MAP), cardiac output (CO), renal blood flow (RBF), glomerular filtration and activity of anti-oxidative enzymes were determined after three weeks treatment. Vibroacustic treatment had no influence on MAP and CO, but RBF was increased in both groups of treated rats. Additionally, vibroacustic treatment enhanced diuresis and increased glomerular filtration in hypertensive rats. Glutathione peroxidase (GSH-Px) activity was elevated in both treated rat strains, but activity of superoxide dismutase was unchanged. We conclude that microvibration treatment doesn't ameliorate hypertension but improves renal blood supply (trough diminished renal vascular resistance), glomerular filtration, diuresis, and enhances glutathione dependent anti-oxidant defense with more important beneficials in hypertensive animals

Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

Acute kidney injury (AKI) is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR) with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance (P lt 0.05) compared to AKI control. It also increased cardiac output and catalase activity (P lt 0.05). Lipid peroxidation and renal vascular resistance were decreased in TEMPOL (P lt 0.05). Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O-2(-) scavenging