TY  - JOUR
AU  - Stojanović, Marko
AU  - Čolović, Mirjana B.
AU  - Lalatović, Jovana
AU  - Milosavljević, Aleksandra
AU  - Savić, Nada D.
AU  - Declerck, Kilian
AU  - Radosavljević, Branimir
AU  - Ćetković, Mila
AU  - Kravić-Stevović, Tamara
AU  - Parac-Vogt, Tatjana N.
AU  - Krstić, Danijela
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12867
AB  - 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.
T2  - International Journal of Molecular Sciences
T1  - Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution
VL  - 25
IS  - 5
SP  - 2569
DO  - 10.3390/ijms25052569
ER  - 

@article{
author = "Stojanović, Marko and Čolović, Mirjana B. and Lalatović, Jovana and Milosavljević, Aleksandra and Savić, Nada D. and Declerck, Kilian and Radosavljević, Branimir and Ćetković, Mila and Kravić-Stevović, Tamara and Parac-Vogt, Tatjana N. and Krstić, Danijela",
year = "2024",
abstract = "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.",
journal = "International Journal of Molecular Sciences",
title = "Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution",
volume = "25",
number = "5",
pages = "2569",
doi = "10.3390/ijms25052569"
}

Stojanović, M., Čolović, M. B., Lalatović, J., Milosavljević, A., Savić, N. D., Declerck, K., Radosavljević, B., Ćetković, M., Kravić-Stevović, T., Parac-Vogt, T. N.,& Krstić, D.. (2024). Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution. in International Journal of Molecular Sciences, 25(5), 2569.
https://doi.org/10.3390/ijms25052569

Stojanović M, Čolović MB, Lalatović J, Milosavljević A, Savić ND, Declerck K, Radosavljević B, Ćetković M, Kravić-Stevović T, Parac-Vogt TN, Krstić D. Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution. in International Journal of Molecular Sciences. 2024;25(5):2569.
doi:10.3390/ijms25052569 .

Stojanović, Marko, Čolović, Mirjana B., Lalatović, Jovana, Milosavljević, Aleksandra, Savić, Nada D., Declerck, Kilian, Radosavljević, Branimir, Ćetković, Mila, Kravić-Stevović, Tamara, Parac-Vogt, Tatjana N., Krstić, Danijela, "Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution" in International Journal of Molecular Sciences, 25, no. 5 (2024):2569,
https://doi.org/10.3390/ijms25052569 . .

TY  - JOUR
AU  - Stojanović, Marko
AU  - Lalatović, Jovana
AU  - Milosavljević, Aleksandra
AU  - Savić, Nada
AU  - Simms, Charlotte
AU  - Radosavljević, Branimir
AU  - Ćetković, Mila
AU  - Kravić Stevović, Tamara
AU  - Mrda, Davor
AU  - Čolović, Mirjana B.
AU  - Parac-Vogt, Tatjana N.
AU  - Krstić, Danijela
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11091
AB  - In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/β-K 6 P 2 W 18 O 62 (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.
T2  - Scientific Reports
T1  - In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography
VL  - 13
IS  - 1
SP  - 9140
DO  - 10.1038/s41598-023-36317-8
ER  - 

@article{
author = "Stojanović, Marko and Lalatović, Jovana and Milosavljević, Aleksandra and Savić, Nada and Simms, Charlotte and Radosavljević, Branimir and Ćetković, Mila and Kravić Stevović, Tamara and Mrda, Davor and Čolović, Mirjana B. and Parac-Vogt, Tatjana N. and Krstić, Danijela",
year = "2023",
abstract = "In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/β-K 6 P 2 W 18 O 62 (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.",
journal = "Scientific Reports",
title = "In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography",
volume = "13",
number = "1",
pages = "9140",
doi = "10.1038/s41598-023-36317-8"
}

Stojanović, M., Lalatović, J., Milosavljević, A., Savić, N., Simms, C., Radosavljević, B., Ćetković, M., Kravić Stevović, T., Mrda, D., Čolović, M. B., Parac-Vogt, T. N.,& Krstić, D.. (2023). In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography. in Scientific Reports, 13(1), 9140.
https://doi.org/10.1038/s41598-023-36317-8

Stojanović M, Lalatović J, Milosavljević A, Savić N, Simms C, Radosavljević B, Ćetković M, Kravić Stevović T, Mrda D, Čolović MB, Parac-Vogt TN, Krstić D. In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography. in Scientific Reports. 2023;13(1):9140.
doi:10.1038/s41598-023-36317-8 .

Stojanović, Marko, Lalatović, Jovana, Milosavljević, Aleksandra, Savić, Nada, Simms, Charlotte, Radosavljević, Branimir, Ćetković, Mila, Kravić Stevović, Tamara, Mrda, Davor, Čolović, Mirjana B., Parac-Vogt, Tatjana N., Krstić, Danijela, "In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography" in Scientific Reports, 13, no. 1 (2023):9140,
https://doi.org/10.1038/s41598-023-36317-8 . .

TY  - CONF
AU  - Dinčić, Marko
AU  - Sarić, Marija
AU  - Čolović, Mirjana
AU  - Todorović, Jasna
AU  - Ignjatović, Svetlana
AU  - Radosavljević, Branimir
AU  - Mougharbel, Ali S.
AU  - Kortz, Ulrich
AU  - Krstić, Danijela
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12962
AB  - Introduction. Polyoxometalates (POMs) are negatively charged inorganic aggregates that possess potential antibacterial, anticancer, antidiabetic and antiviral effects. Although toxicity evaluation of drug candidates is necessary, reports of relevant toxicological studies of these compounds are relatively rare.  Aims. Since our preliminary results demonstrated biological activities of the donut-shaped POM {NaP5W30} (POM1) and the Ag + -containing derivative POM {AgP5W30} (POM2), the aim of present study was to evaluate their toxicological effects in vivo, using Wistar albino rats as an experimental model.  Methods. Animals (n = 6 per group) were orally treated with investigated POMs in daily doses of 20 mg/kg body weight for 14 days when the rats were sacrificed and blood samples were collected. The biochemical markers of renal (serum concentrations of urea - SUr and creatinine - SCr) and liver function (serum concentrations of total protein–TP and albumin - Alb, serum activities of aspartate aminotransferase - AST and alanine transaminase - ALT) were determined spectrophotometrically.  Results. The POM1 and POM2 were induced statistically significant increasing of SUr (in: mmol/L) (7.95 ± 0.35 and 6.83 ± 0.26 vs. 4.97 ± 0.47; p < 0.001 and p < 0.01, respectively) and SCr (in: mmol/L) (41.34 ± 0.84 and 39.06 ± 1.07 vs. 32.27 ± 0.61; p < 0.001 and p < 0.001, respectively) compared to the control group. Also, investigated compounds induced statistically significant decreasing of TP (in: g/L) (60.16 ± 1.43 and 58.53 ± 0.81 vs. 67.86 ± 0.03; p < 0.001 and p < 0.001, respectively) and Alb (in: g/L) (29.34 ± 0.58 and 29.45 ± 0.81 vs. 34.89 ± 0.41; p < 0.001 and p < 0.001, respectively) compared to the control group. In contrast, there was no statistically significant difference in AST and ALT between the untreated and treated groups (p > 0.05).  Conclusion. Obtained results suggested that both investigated POMs induce kidney injury as well as synthetic dysfunction of liver. Thus, their potential clinical application would require a more complex toxicological study.
C3  - Pathophysiology
T1  - Toxicity evaluation of two biologically active polyoxotungstates
VL  - 25
IS  - 3
SP  - 243
EP  - 244
DO  - 10.1016/j.pathophys.2018.07.177
ER  - 

@conference{
author = "Dinčić, Marko and Sarić, Marija and Čolović, Mirjana and Todorović, Jasna and Ignjatović, Svetlana and Radosavljević, Branimir and Mougharbel, Ali S. and Kortz, Ulrich and Krstić, Danijela",
year = "2018",
abstract = "Introduction. Polyoxometalates (POMs) are negatively charged inorganic aggregates that possess potential antibacterial, anticancer, antidiabetic and antiviral effects. Although toxicity evaluation of drug candidates is necessary, reports of relevant toxicological studies of these compounds are relatively rare.  Aims. Since our preliminary results demonstrated biological activities of the donut-shaped POM {NaP5W30} (POM1) and the Ag + -containing derivative POM {AgP5W30} (POM2), the aim of present study was to evaluate their toxicological effects in vivo, using Wistar albino rats as an experimental model.  Methods. Animals (n = 6 per group) were orally treated with investigated POMs in daily doses of 20 mg/kg body weight for 14 days when the rats were sacrificed and blood samples were collected. The biochemical markers of renal (serum concentrations of urea - SUr and creatinine - SCr) and liver function (serum concentrations of total protein–TP and albumin - Alb, serum activities of aspartate aminotransferase - AST and alanine transaminase - ALT) were determined spectrophotometrically.  Results. The POM1 and POM2 were induced statistically significant increasing of SUr (in: mmol/L) (7.95 ± 0.35 and 6.83 ± 0.26 vs. 4.97 ± 0.47; p < 0.001 and p < 0.01, respectively) and SCr (in: mmol/L) (41.34 ± 0.84 and 39.06 ± 1.07 vs. 32.27 ± 0.61; p < 0.001 and p < 0.001, respectively) compared to the control group. Also, investigated compounds induced statistically significant decreasing of TP (in: g/L) (60.16 ± 1.43 and 58.53 ± 0.81 vs. 67.86 ± 0.03; p < 0.001 and p < 0.001, respectively) and Alb (in: g/L) (29.34 ± 0.58 and 29.45 ± 0.81 vs. 34.89 ± 0.41; p < 0.001 and p < 0.001, respectively) compared to the control group. In contrast, there was no statistically significant difference in AST and ALT between the untreated and treated groups (p > 0.05).  Conclusion. Obtained results suggested that both investigated POMs induce kidney injury as well as synthetic dysfunction of liver. Thus, their potential clinical application would require a more complex toxicological study.",
journal = "Pathophysiology",
title = "Toxicity evaluation of two biologically active polyoxotungstates",
volume = "25",
number = "3",
pages = "243-244",
doi = "10.1016/j.pathophys.2018.07.177"
}

Dinčić, M., Sarić, M., Čolović, M., Todorović, J., Ignjatović, S., Radosavljević, B., Mougharbel, A. S., Kortz, U.,& Krstić, D.. (2018). Toxicity evaluation of two biologically active polyoxotungstates. in Pathophysiology, 25(3), 243-244.
https://doi.org/10.1016/j.pathophys.2018.07.177

Dinčić M, Sarić M, Čolović M, Todorović J, Ignjatović S, Radosavljević B, Mougharbel AS, Kortz U, Krstić D. Toxicity evaluation of two biologically active polyoxotungstates. in Pathophysiology. 2018;25(3):243-244.
doi:10.1016/j.pathophys.2018.07.177 .

Dinčić, Marko, Sarić, Marija, Čolović, Mirjana, Todorović, Jasna, Ignjatović, Svetlana, Radosavljević, Branimir, Mougharbel, Ali S., Kortz, Ulrich, Krstić, Danijela, "Toxicity evaluation of two biologically active polyoxotungstates" in Pathophysiology, 25, no. 3 (2018):243-244,
https://doi.org/10.1016/j.pathophys.2018.07.177 . .

TY  - JOUR
AU  - Krstić, Danijela Z.
AU  - Tomić, Nenad
AU  - Radosavljević, Branimir
AU  - Avramović, Nataša
AU  - Dragutinović, Vesna
AU  - Radojević-Škodrić, Sanja
AU  - Čolović, Mirjana B.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1200
AB  - Kidney damage can be induced by ischemia, autoimmune diseases, hypertension, allograft rejection, metabolic or genetic disorders, infections or toxins. The influence of these factors could result in acute kidney injury (AKI) defined as an unexpected decrease in urine output or renal function, or encourage the development of chronic kidney disease (CKD). Biomarkers of renal function, measured in urine and serum, are in increasing use in order to estimate the severity and nature of kidney injury, and consequently apply appropriate therapy and improve patient management. The determined values of biomarkers can suggest the potential risk of kidney disease and the type of renal injury, predict the disease progression, as well as be helpful for assessing the response to an applied therapy. Although novel biomarkers are in practical use, serum creatinine, the indicator of glomerular filtration rate is still the most frequently used biomarker of renal function despite its known limitations. In recent decades, numerous studies resulted in discovering urinary and serum proteins that can serve as biomarkers for early and accurate detection of AKI and its development, as well as the identification of CKD. This review gives an overview of the most important renal biomarkers investigated in kidney diseases, classified in following types: functional biomarkers, up-regulated proteins, enzymes, and cycle arrest biomarkers. It describes their properties, physiological roles, and discusses the utility of these molecules in different clinical settings.
T2  - Current Medicinal Chemistry
T1  - Biochemical Markers of Renal Function
VL  - 23
IS  - 19
SP  - 2018
EP  - 2040
DO  - 10.2174/0929867323666160115130241
ER  - 

@article{
author = "Krstić, Danijela Z. and Tomić, Nenad and Radosavljević, Branimir and Avramović, Nataša and Dragutinović, Vesna and Radojević-Škodrić, Sanja and Čolović, Mirjana B.",
year = "2016",
abstract = "Kidney damage can be induced by ischemia, autoimmune diseases, hypertension, allograft rejection, metabolic or genetic disorders, infections or toxins. The influence of these factors could result in acute kidney injury (AKI) defined as an unexpected decrease in urine output or renal function, or encourage the development of chronic kidney disease (CKD). Biomarkers of renal function, measured in urine and serum, are in increasing use in order to estimate the severity and nature of kidney injury, and consequently apply appropriate therapy and improve patient management. The determined values of biomarkers can suggest the potential risk of kidney disease and the type of renal injury, predict the disease progression, as well as be helpful for assessing the response to an applied therapy. Although novel biomarkers are in practical use, serum creatinine, the indicator of glomerular filtration rate is still the most frequently used biomarker of renal function despite its known limitations. In recent decades, numerous studies resulted in discovering urinary and serum proteins that can serve as biomarkers for early and accurate detection of AKI and its development, as well as the identification of CKD. This review gives an overview of the most important renal biomarkers investigated in kidney diseases, classified in following types: functional biomarkers, up-regulated proteins, enzymes, and cycle arrest biomarkers. It describes their properties, physiological roles, and discusses the utility of these molecules in different clinical settings.",
journal = "Current Medicinal Chemistry",
title = "Biochemical Markers of Renal Function",
volume = "23",
number = "19",
pages = "2018-2040",
doi = "10.2174/0929867323666160115130241"
}

Krstić, D. Z., Tomić, N., Radosavljević, B., Avramović, N., Dragutinović, V., Radojević-Škodrić, S.,& Čolović, M. B.. (2016). Biochemical Markers of Renal Function. in Current Medicinal Chemistry, 23(19), 2018-2040.
https://doi.org/10.2174/0929867323666160115130241

Krstić DZ, Tomić N, Radosavljević B, Avramović N, Dragutinović V, Radojević-Škodrić S, Čolović MB. Biochemical Markers of Renal Function. in Current Medicinal Chemistry. 2016;23(19):2018-2040.
doi:10.2174/0929867323666160115130241 .

Krstić, Danijela Z., Tomić, Nenad, Radosavljević, Branimir, Avramović, Nataša, Dragutinović, Vesna, Radojević-Škodrić, Sanja, Čolović, Mirjana B., "Biochemical Markers of Renal Function" in Current Medicinal Chemistry, 23, no. 19 (2016):2018-2040,
https://doi.org/10.2174/0929867323666160115130241 . .