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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
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
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/3495
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Institution
Pharmacy

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