Effect of thermal stress of short duration on the red blood cell parameters of Barbus balcanicus Kotlik, Tsigenopulos, Rab, Berrebi, 2002

In this study, red blood cell parameters of Barbus balcanicus Kotlik, Tsigenopulos, Rab, Berrebi, 2002 subjected to acute thermal stress were investigated. Fish were caught by electro fishing in the Suturlija river, a small tributary of the river Vrbas (N latitude 44˚44' 38˝, E longitude 17˚ 09' 10˝) in summer (July) and transported to the laboratory. Fish were randomly distributed in four aquaria of 30 L each. In all the four aquaria, the water temperature was continuously kept at 19°C by appropriate devices. After period of adaptation (three weeks), half of the fish (24) were used as a control group while the other 24 were subjected to thermal stress by raising the water temperature to 29°C (10°C increase) in 60 min. In both control and thermally treated, fish blood was collected by heart puncture according to “Animal welfare act“. Analyses were performed with native blood, without addition of any anticoagulant and the values of red blood cell count (RBC), haemoglobin concentration, packed cell volume (PCV), Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and Mean Corpuscular Haemoglobin Concentration (MCHC) were determined. In the thermally treated fish, the values of PCV and MCV increased (p = 0.0003 and p = 0.0147 respectively), and those of MCHC decreased substantially (p = 0.0001).Keywords: Haematology, temperature, Barbus balcanicusAfrican Journal of Biotechnology Vol. 12(18), pp. 2484-249

Razvoj novih antidijabetičkih lekova na bazi polioksometalatnih nanoklastera

Zahvaljujući brojnim istraživanjima koja su ispitivala biološka svojstva strukturno različitih polioksometalata, došlo se do zapažanja da ova kompleksna neorganska jedinjenja, pored antimikrobnog i antitumorskog delovanja, mogu biti delotvorna u snižavanju hiperglikemije kod pacova sa eksperimentalno izazvanim dijabetesom. Stoga, cilj ove studije je bio da se ispitaju antidijabetički potencijal i mogući toksični efekti dva polioksovolframata:(NH4 )14[NaP5 W30O110]·31H2 O, {NaP5 W30} i K14[AgP5 W30O110]·22H2 O·6KCl, {AgP5 W30}. U cilju realizacije postavljenog cilja, korišćena su tri eksperimentalna modela: (1) antihiperglikemijska screening studija u kojoj je ispitivan uticaj jednokratne intraperitonealne primene {NaP5 W30} i {AgP5 W30} (5, 10 i 20 mg/kg) na snižavanje hiperglikemije kod dijabetičkih pacova, (2) akutna peroralna toksikološka studija koja je istraživala hepato- i nefrotoksične efekte odabranih heteropolivolframata kod zdravih pacova i (3) studija posvećena rasvetljavanju mogućih mehanizama antidijabetičkog delovanja heteropolivolframata. Rezultati screening studije su pokazali da su oba ispitivana heteropolivolframata efikasna u snižavanju hiperglikemije, s tim što se {NaP5 W30}, u odnosu na {AgP5 W30}, pokazao kao moćniji antihiperglikemijski agens. Rezultati biohemijskih parametara funkcije i patohistološka analiza jetre i bubrege korišćenjem konvencionalne svetlosne i transmisione elektronske mikroskopije pokazuju da dvonedeljna primena {NaP5 W30} i {AgP5 W30} (20 mg/kg) izaziva blagi do umereni stepen hepato- i nefrotoksičnosti kod zdravih životinja. U poslednjem eksperimentalnom protokolu, pokazano je da tronedeljna peroralna primena {NaP5 W30} (20 mg/kg) povećava koncentraciju insulina u serumu dijabetičkih pacova, što može biti jedan od mehanizama njegovog antidijabetičkog delovanja. Takođe, pokazano je da {NaP5 W30} ispoljava hepato-, nefro-, kardio- i neuroprotektivno dejstvo kod dijabetičkih pacova, što je procenjeno na osnovu analize: (1) relativne mase organa, (2) biohemijskih parametara funkcije, (3) parametara oksidativnog stresa u homogenatu tkiva, (4) aktivnosti acetilholinesteraze, Na+ /K+-ATPaze i ecto-ATPaza u sinaptozomima i (5) patohistoloških promena u tkivima korišćenjem konvencionalne svetlosne i transmisione elektronske mikroskopije. Stoga, {NaP5 W30} i {AgP5 W30} mogu se smatrati mogućim neinsulinskim lekovima-kandidatima u terapiji dijabetesa tipa 2, koji bi se podvrgli daljim pretkliničkim istraživanjima.Simpozijum „Stremljenja i novine u medicini“ Medicinskog fakulteta u Beogradu, Beograd, 04-08. decembra, 2023

Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells–Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats’ general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD—0.67 ± 0.12; 1/5 MAD—0.59 ± 0.07; 1/10 MAD—0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels

In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography

Abstract In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/β-K6P2W18O62 (WD-POM) exhibits superior performance as a computed tomography (CT) contrast agent, in comparison to the standard contrast agent iohexol. A toxicity evaluation of WD-POM was performed according to standard toxicological protocols using Wistar albino rats. The maximum tolerable dose (MTD) of 2000 mg/kg was initially determined after oral WD-POM application. The acute intravenous toxicity of single WD-POM doses (1/3, 1/5, and 1/10 MTD), which are at least fifty times higher than the typically used dose (0.015 mmol W kg−1) of tungsten-based contrast agents, was evaluated for 14 days. The results of arterial blood gas analysis, CO-oximetry status, electrolyte and lactate levels for 1/10 MTD group (80% survival rate) indicated the mixed respiratory and metabolic acidosis. The highest deposition of WD-POM (0.6 ppm tungsten) was found in the kidney, followed by liver (0.15 ppm tungsten), for which the histological analysis revealed morphological irregularities, although the renal function parameters (creatinine and BUN levels) were within the physiological range. This study is the first and important step in evaluating side effects of polyoxometalate nanoclusters, which in recent years have shown a large potential as therapeutics and contrast agents

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system

In this study, thein vivohypoglycemic effect of a donut-shaped polyanion salt (NH4)14[Na@P5W30O110]$31H2O{NaP5W30} and its Ag-containing derivative K14[Ag@P5W30O110]$22H2O$6KCl {AgP5W30}, as wellas their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study,Wistaralbinorats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5,10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels,measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studiedcompounds induced the most pronounced and time dependent glucose lowering effects at the doses of20 mg kg1. Thus, daily doses of 20 mg kg1were administered toWistar albinorats orally for 14 days infurther toxicity examinations. The serum glucose concentration and biochemical parameters of kidneyand liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14days after the polyoxotungstate administration. Both investigated compounds did not induce statisticallysignificant alterations of the serum glucose and uric acid concentrations, as well as some of the liverfunction markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities).However, the significant decrease in serum total protein and albumin concentrations and the increase inbiochemical parameters of renal function–serum urea (up to 63.1%) and creatinine concentrations (upto 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changeswere in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic andnephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild