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Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity

Authorized Users Only
2017
Authors
Čolović, Mirjana B.
Medic, Branislava
Cetkovic, Mila
Kravić-Stevović, Tamara K.
Stojanović, Marko
Ayass, Wassim W.
Mougharbel, Ali S.
Radenković, Miroslav
Prostran, Milica
Kortz, Ulrich
Krstić, Danijela Z.
Article (Published version)
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Abstract
A toxicity evaluation of two Keggin-type heteropolytungstates, K-7[Ti2PW10O40].6H(2)O and K6H [SiV3W9O40].3H(2)O, with different inhibitory potencies toward acetylcholinesterase activity (IC50 values of 1.04 x 10(-6) and 4.80 x 10(-4) mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50 mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24 h and 14 days. A histopathological analysis of liver tissue was carried out 14 days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration -depe...ndent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K6H [SiV3W9O40]-3H(2)O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.

Keywords:
acetylcholinesterase / Biochemical parameters / Hepatotoxicity / Histopathological analysis / Polyoxometalates / Renal function
Source:
Toxicology and Applied Pharmacology, 2017, 333, 68-75
Funding / projects:
  • Studies of enzyme interactions with toxic and pharmacologically active molecules (RS-172023)
  • Basic and Clinical Pharmacological research of mechanisms of action and drug interactions in nervous and cardiovascular system (RS-175023)

DOI: 10.1016/j.taap.2017.08.010

ISSN: 0041-008X; 1096-0333

PubMed: 28830837

WoS: 000411549600009

Scopus: 2-s2.0-85027992887
[ Google Scholar ]
11
6
URI
https://vinar.vin.bg.ac.rs/handle/123456789/1748
Collections
  • WoS Import
Institution/Community
Vinča
TY  - JOUR
AU  - Čolović, Mirjana B.
AU  - Medic, Branislava
AU  - Cetkovic, Mila
AU  - Kravić-Stevović, Tamara K.
AU  - Stojanović, Marko
AU  - Ayass, Wassim W.
AU  - Mougharbel, Ali S.
AU  - Radenković, Miroslav
AU  - Prostran, Milica
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1748
AB  - A toxicity evaluation of two Keggin-type heteropolytungstates, K-7[Ti2PW10O40].6H(2)O and K6H [SiV3W9O40].3H(2)O, with different inhibitory potencies toward acetylcholinesterase activity (IC50 values of 1.04 x 10(-6) and 4.80 x 10(-4) mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50 mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24 h and 14 days. A histopathological analysis of liver tissue was carried out 14 days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration -dependent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K6H [SiV3W9O40]-3H(2)O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.
T2  - Toxicology and Applied Pharmacology
T1  - Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity
VL  - 333
SP  - 68
EP  - 75
DO  - 10.1016/j.taap.2017.08.010
ER  - 
@article{
author = "Čolović, Mirjana B. and Medic, Branislava and Cetkovic, Mila and Kravić-Stevović, Tamara K. and Stojanović, Marko and Ayass, Wassim W. and Mougharbel, Ali S. and Radenković, Miroslav and Prostran, Milica and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2017",
abstract = "A toxicity evaluation of two Keggin-type heteropolytungstates, K-7[Ti2PW10O40].6H(2)O and K6H [SiV3W9O40].3H(2)O, with different inhibitory potencies toward acetylcholinesterase activity (IC50 values of 1.04 x 10(-6) and 4.80 x 10(-4) mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50 mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24 h and 14 days. A histopathological analysis of liver tissue was carried out 14 days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration -dependent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K6H [SiV3W9O40]-3H(2)O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.",
journal = "Toxicology and Applied Pharmacology",
title = "Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity",
volume = "333",
pages = "68-75",
doi = "10.1016/j.taap.2017.08.010"
}
Čolović, M. B., Medic, B., Cetkovic, M., Kravić-Stevović, T. K., Stojanović, M., Ayass, W. W., Mougharbel, A. S., Radenković, M., Prostran, M., Kortz, U.,& Krstić, D. Z.. (2017). Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity. in Toxicology and Applied Pharmacology, 333, 68-75.
https://doi.org/10.1016/j.taap.2017.08.010
Čolović MB, Medic B, Cetkovic M, Kravić-Stevović TK, Stojanović M, Ayass WW, Mougharbel AS, Radenković M, Prostran M, Kortz U, Krstić DZ. Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity. in Toxicology and Applied Pharmacology. 2017;333:68-75.
doi:10.1016/j.taap.2017.08.010 .
Čolović, Mirjana B., Medic, Branislava, Cetkovic, Mila, Kravić-Stevović, Tamara K., Stojanović, Marko, Ayass, Wassim W., Mougharbel, Ali S., Radenković, Miroslav, Prostran, Milica, Kortz, Ulrich, Krstić, Danijela Z., "Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity" in Toxicology and Applied Pharmacology, 333 (2017):68-75,
https://doi.org/10.1016/j.taap.2017.08.010 . .

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