TY  - JOUR
AU  - Dinčić, Marko
AU  - Čolović, Mirjana B.
AU  - Sarić Matutinović, Marija
AU  - Ćetković, Mila
AU  - Kravić-Stevović, Tamara K.
AU  - Mougharbel, Ali S.
AU  - Todorović, Jasna
AU  - Ignjatović, Svetlana
AU  - Radosavljević, Branimir
AU  - Milisavljević, Milan
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8479
AB  - 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.
T2  - RSC Advances
T1  - In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system
VL  - 10
IS  - 5
SP  - 2846
EP  - 2855
DO  - 10.1039/C9RA09790B
ER  - 

@article{
author = "Dinčić, Marko and Čolović, Mirjana B. and Sarić Matutinović, Marija and Ćetković, Mila and Kravić-Stevović, Tamara K. and Mougharbel, Ali S. and Todorović, Jasna and Ignjatović, Svetlana and Radosavljević, Branimir and Milisavljević, Milan and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2020",
abstract = "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.",
journal = "RSC Advances",
title = "In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system",
volume = "10",
number = "5",
pages = "2846-2855",
doi = "10.1039/C9RA09790B"
}

Dinčić, M., Čolović, M. B., Sarić Matutinović, M., Ćetković, M., Kravić-Stevović, T. K., Mougharbel, A. S., Todorović, J., Ignjatović, S., Radosavljević, B., Milisavljević, M., Kortz, U.,& Krstić, D. Z.. (2020). In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system. in RSC Advances, 10(5), 2846-2855.
https://doi.org/10.1039/C9RA09790B

Dinčić M, Čolović MB, Sarić Matutinović M, Ćetković M, Kravić-Stevović TK, Mougharbel AS, Todorović J, Ignjatović S, Radosavljević B, Milisavljević M, Kortz U, Krstić DZ. In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system. in RSC Advances. 2020;10(5):2846-2855.
doi:10.1039/C9RA09790B .

Dinčić, Marko, Čolović, Mirjana B., Sarić Matutinović, Marija, Ćetković, Mila, Kravić-Stevović, Tamara K., Mougharbel, Ali S., Todorović, Jasna, Ignjatović, Svetlana, Radosavljević, Branimir, Milisavljević, Milan, Kortz, Ulrich, Krstić, Danijela Z., "In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system" in RSC Advances, 10, no. 5 (2020):2846-2855,
https://doi.org/10.1039/C9RA09790B . .

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 . .