Tag Archives: toxicity
Multifunctional chitosan-based hydrogels: characterization and evaluation of biocompatibility and biodegradability in vitro
N. Manko1, M. Lootsik1, V. Antonyuk1,2, I. Ivasechko1,
N. Skorokhyd1, H. Kosiakova3, O. Mehed’3, T. Horid’ko3,
N. Hula3, O. Klyuchivska1, R. Panchuk1, N. Pokhodylo4,
О. Barabash4, T. Dumych2, R. Stoika1,4*
1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Danylo Halytsky National Medical University of Lviv, Lviv, Ukraine;
3Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
4Ivan Franko National University of Lviv, Lviv, Ukraine;
*e-mail: stoika.rostyslav@gmail.com
Received: 29 November 2023; Revised: 31 December 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024
Creation of novel remedies efficient in supporting wound healing remains an actual task in pharmacology. Hydrogels showed high efficiency in wound healing and tissue regeneration due to viscosity, elasticity and fluidity that provide them with functional characteristics similar to that in extracellular matrix. The aim of the study was to create chitosan-based hydrogels functionalized with different components (chondroitin-6-sulfate, hyaluronic acid, N-stearoylethanolamine) and to estimate their biocompatibility and biodegradability in vitro. For the first time, a lipid substance N-stearoylethanolamine (NSE) known as suppressor of pro-inflammatory cytokines expression was used as hydrogel component (1.95 mg/g). FTIR analysis confirmed the complexation of chitosan molecule with hyaluronate, chondroitin-6-sulfate, NSE. MTT-test and Trypan blue exclusion test were used to study hydrogels cytotoxicity towards human cells of different tissue origin. Biodegradability of hydrogels was evaluated using direct hydrogel contact with cells and cell-independent degradation. It was shown that chondroitin-6-sulfate (<2 mg/ml), hyaluronic acid (<2 mg/ml) and NSE (26 µg/ml) did not demonstrate significant toxic effects towards pseudonormal human cells of the MCF10A, HaCat, HEK293 lines and mouse cells of the Balb/3T3 line. The studied hydrogels were stable in saline solution, while in a complete culture medium containing 10% fetal bovine blood serum they underwent degradation in >24 h. The identified biodegradability of the chitosan-based hydrogels is important for the release of noncovalently immobilized NSE into biological medium. Further studies on laboratory animals with experimental wounds are expected to explore the potential of created hydrogels as anti-inflammatory and wound-healing agents.
Biochemical mechanisms of free-radical damage to the nuclear genome by cadmium
I. M. Trakhtenberg1, Y. I. Gubsky2, E. L. Levitsky3, I. F. Belenichev4
1Institute of Occupational Medicine, National Academy of Medical Sciences of Ukraine, Kyiv;
2Insitute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv;
3Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: levitsky@biochem.kiev.ua;
4Zaporozhye State Medical University of the Ministry of Health of Ukraine
Cadmium, has been used for many years in industry and agriculture. Its active use is associated with a danger to human health due to a significant toxic effect on the body. The purpose of the review was to analyze the literature data and the results of our own experimental research on the biochemical mechanisms of the toxic effect of cadmium on the nuclear chromatin of cells, primarily the liver. Based on this analysis, the concept that the toxicity of cadmium is associated with damage caused by cadmium-induced free radicals was confirmed. The reactive oxygen species formed in this way are active damaging agents that cause toxic effects, including mutagenic, which ultimately leads to apoptosis and cell death.
Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity
O. M. Kozachkova1, N. V. Tsaryk1, V. V. Trachevskyi2,
A. B. Rozhenko3, Yu. H. Shermolovich3, O. I. Guzyr3,
N. I. Sharykina4, V. F. Chekhun5, V. I. Pekhnyo1
1Vernadsky Institute of General and Inorganic Chemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Technical Centre of National Academy of Sciences of Ukraine, Kyiv;
3Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
4SI “Institute of Pharmacology and Toxicology, National Academy
of Medical Sciences of Ukraine”, Kyiv;
5Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
e-mail: complex@ionc.kiev.ua
Complex formation of K2[PdCl4] with 1-phenyl-1-hydroxymethylene bisphosphonic acid (PhHMBP, H4L) has been studied by pH potentiometry, electron and NMR spectroscopy. It was found that in aqueous solution with physiological concentration of chlorine anions (0.15 mol/l KCl), anionic complexes of the equimolar compositions [PdHLCl2]3- (lgβ = 24.51 (0.3)) and [PdLCl2]4- (lgβ = 20.74 (0.02)) are formed. In the first coordination sphere palladium was surrounded by two oxygen atoms of two phosphonic groups of the bidentately coordinated ligand with closure of six-membered [O, O] ring, and two chlorine anions. The formation of palladium(II) equimolar complexes with PhHMBP and bidentate coordination of the ligand to the central metal cation was confirmed by 31P NMR spectroscopy. Cytotoxic activity (IC50 based on metal content) of the synthesized Pd(II) complexes with PhHMBP against human MG-63 osteosarcoma and MCF-7 mammary tumor cells was compared with cisplatin on in vitro models. It was established that cytotoxic activity of the Pd complexes was lower than that of cisplatin. The acute toxicity (LD50 based on metal content) of solutions of Pd(II) complexes with PhHMBP was found to be lower compared to cisplatin. It was shown that the use of solutions of palladium(II) complexes with PhHMBP inhibited tumor growth in mice with sarcoma 180.
Antioxidant activity of alkoxy derivatives of (quinoline-4-ylthio)carboxylic acids
O. О. Brazhko1, M. P. Zavgorodny1, O. S. Kruglyak2,
L. O. Omeljanchik1, G. A. Shapoval2
1Zaporizhzhya National University, Ukraine;
2Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: hellen.brazhko@gmail.com
A selection of potential bioactive molecules including alkoxy derivatives of (quinoline-4-ylthio)carboxylic acids using virtual screening has been carried out and their biological activity was determined. The studied substances proved to be low-toxic, biologically active compounds. It was established that 4-thio derivatives of quinoline exhibit pronounced antiradical, antioxidant effects and can act as preventive antioxidants, radio and cytoprotectors.