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

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2020
In_vivo_toxicity_pub_2020.pdf (1.385Mb)
Authors
Dinčić, Marko
Čolović, Mirjana B.
Sarić-Matutinović, Marija
Ćetković, Mila
Kravić Stevović, Tamara
Mougharbel, Ali S.
Todorović, Jasna
Ignjatović, Svetlana
Radosavljević, Branimir
Milisavljević, Milan
Kortz, Ulrich
Krstić, Danijela Z.
Article (Published version)
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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 af...ter 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.

Keywords:
Alkalinity / Amino acids / Glucose / Phosphatases / Rats / Toxicity / Urea
Source:
RSC Advances, 2020, 10, 5, 2846-2855
Publisher:
  • Royal Society of Chemistry
Funding / projects:
  • Studies of enzyme interactions with toxic and pharmacologically active molecules (RS-172023)
  • Biomarkers of organ damage and dysfunction (RS-175036)
  • Project Serbia–Germany (no. 451-03-01038/2015-09/16, DAAD-PP)
  • MST COST Action CM1203(PoCheMoN)

DOI: 10.1039/c9ra09790b

ISSN: 2046-2069

WoS: 000512409400046

Scopus: 2-s2.0-85078495117
[ Google Scholar ]
3
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3495
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Dinčić, Marko
AU  - Čolović, Mirjana B.
AU  - Sarić-Matutinović, Marija
AU  - Ćetković, Mila
AU  - Kravić Stevović, Tamara
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://farfar.pharmacy.bg.ac.rs/handle/123456789/3495
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.
PB  - Royal Society of Chemistry
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 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.",
publisher = "Royal Society of Chemistry",
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., 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
Royal Society of Chemistry., 10(5), 2846-2855.
https://doi.org/10.1039/c9ra09790b
Dinčić M, Čolović MB, Sarić-Matutinović M, Ćetković M, Kravić Stevović T, 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, 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 . .

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