Tag Archives: aspartate aminotransferase
Iodide n,π-chelate complexes of platinum(II) based on N-allyl substituted thioureas and their effect on the activity of hepatobiliary system enzymes in comparison with chloride analogs
V. Orysyk1*, L. Garmanchuk2, S. Orysyk3, Yu. Zborovskii1,
S. Shishkina4, I. Stupak2, P. Novikova3, D. Ostapchenko2,
N. Khranovska5, V. Pekhnyo3, M. Vovk1
1Department of Functional Heterocyclic Systems Chemistry,
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
2Department of Biomedicine of Taras Shevchencko National University,
Educational and Scientific Centre “Institute of Biology and Medicine”, Kyiv, Ukraine
3Department of Complex Compounds Chemistry, V.I. Vernadsky Institute of General
and Inorganic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
4Department of X-ray Diffraction Studies and Quantum Chemistry,
SSI “Institute for Single Crystals”, National Academy of Sciences of Ukraine, Kharkiv;
5National Cancer Institute, Kyiv, Ukraine;
*e-mail: vis.viktorys@gmail.com
Received: 21 December 2023; Revised: 30 January 2024;
Accepted: 31 May 2024; Available on-line: 17 June 2024
The search for new effective drugs in the treatment of neoplasm remains relevant even today, since the adaptation of transformed cells to the action of classical drugs contributes to the emergence of drug resistance. This applies to a number of classic chemotherapy drugs of the platinum series, in particular cisplatin. In this work, we describe the effect of novel analogs of cisplatin on HepG2 cells and on the key enzyme of antioxidant protection system gammaglutamyltranspeptidase, which plays an important role in the acquisition of drug resistance to anticancer drugs by tumor cells. New mononuclear iodide n,π-chelate complexes of Pt(II) with substituted thioureas N-allylmorpholine-4-carbothioamide or 3-allyl-1,1-diethylthiourea were obtained as analogs of cisplatin. All compounds were investigated by UV-Vis, IR, and 1H/13С NMR spectra. Complex I was described by single-crystal X-ray diffraction study. Also, the effect of these analogs on alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, which are marker enzymes of liver cells, release of which into the blood indicates liver pathologies, was investigated. All studies were carried out in comparison with chloride n,π-chelate complexes of platinum obtained earlier (however, the effect of these chloride analogs of platinum on enzymes of the hepatobiliary system was investigated for the first time in this work). The results have shown that the studied compounds are better cytostatics/cytotoxics than cisplatin both according to IC50 and apoptosis level of HepG2 cells. It is established that, for the most part, effect of the studied complexes is reduced to a decrease in the degree of malignancy of cells of hepatocyte lines and the activity of LDH and GHT, as well as a decrease in consumed glucose.
ТiО(2) hepatotoxicity under long-term administration to rats
O. V. Tsymbalyuk, S. P. Veselsky, A. M. Naumenko, T. L. Davydovska,
I. S. Voiteshenko, I. I. Сhyzh, V. A. Skryshevsky
Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: otsymbal@bigmir.net
Received: 30 March 2020; Accepted: 15 May 2020
Titanium dioxide (ТіО2) powder which is used as a white dye was considered to be an inert material for a long time despite its accumulation in liver tissues after penetration into organism. The aim of the study was to estimate biochemical markers of liver functioning in blood plasma and ATPase activity of erythrocyte plasma membrane under the oral administration of ТіО2 nanoparticles suspension (0.1 mg/kg, daily) to Wistar rats for 30 and 100 days. A significant increase of alanine aminotransferase and aspartate aminotransferase activity as well as of direct, indirect and bound bilirubin content, a decrease of connjugated (taurocholic, taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic) and free (glycodeoxycholic and deoxycholic) bile acids concentration with concomitant increase of free cholic acid concentration in blood plasma of rats under ТіО2 administration were revealed, indicating a significant impairment of pigment exchange in the liver of rats. Under ТіО2 administration a substantial inhibition of erythrocyte plasma membrane Мg2+-dependent ouabain-sensitive Na+,K+-ATPase and ouabain-insensitive ATPase was observed. These results presume the disturbance of transplasmalema ion-transporting processes and cells ionic homeostasis induced by ТіО2.
Comparison of blood biochemical indices in rats exposed to lead in macrodispersed form and nanoform
I. A. Lazarenko, N. M. Melnikova
National University of Life and Environmental Sciences of Ukraine, Kyiv;
e-mail: ilazarenko2009@yandex.ru
It is shown that the increasing content of lead in blood (6.3 and 3.7 times) and liver (30.1 and 4.6 times) in rats after 14-days per os exposure both to lead acetate (macrodispersed form) and lead nanoparticles (nanoform) in a dose of 7 mg/100 g of body weight leads to the increased of activity of blood enzymes: alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, alkaline phosphatase, lactate dehydrogenase and a decrease of creatinine level. Lead in nanoform with slight accumulation, due to the greater elimination, expressed higher biological activity and reactivity as compared to macrodispersed form. Thus the exposure to lead in different dispersed form suggests metabolic disorders in rats, and accumulation of lead and biochemical changes are more expressed in the liver.