Volodymyr Rybalchenko

Comparative study of membranotropic action of single- and multi-walled carbon nanotubes

The aim of the present work is the investigation of the interactions of single-walled and multi-walled carbon nanotubes (further referred as SWCNTs and MWCNTs, respectively) with bimolecular lipid model membrane (BLM) and cellular plasma membrane (PM). The findings demonstrate that both SWCNTs and MWCNTs (in concentration range of 10⁻⁴ to 10⁻¹ mg ml⁻¹) are capable to penetrate through the region of hydrophobic fatty acid residues of phospholipids and to form molecular associates in the bilayer that have conductive properties of molecular pores type. The formed pores were shown to enable phosphatidylserine externalization from inner to outer PM leaflet. Both types of CNTs increase the specific conductivity and decrease the specific capacity of BLM.

Effect of iron-doped multi-walled carbon nanotubes on lipid model and cellular plasma membranes

The aim of the present work was the study of the interaction of multi-walled carbon nanotubes filled with iron (Fe-MWCNTs) with bimolecular lipid model membrane (BLM) and cellular plasma membrane (PM). The findings demonstrate that the Fe-MWCNTs adsorb on the BLM surface with possible partial build up in the hydrophobic area of fatty acid residues of lipids and increase its specific conductivity and capacity. Furthermore, upon interaction with the PM, the Fe-MWCNTs form channels which allow the flow of water to the cells and the externalization of phosphatidylserine from the inner to the outer PM leaflet.

Activation of aerobic metabolism by Amaranth oil improves heart rate variability both in athletes and patients with type 2 diabetes mellitus

The aim of present research was to study the effects of Amaranth oil (AmO) supplementation on aerobic metabolism and heart rate variability (HRV) in type 2 diabetes mellitus patients and in athletes. Several parameters of aerobic metabolism and HRV were assessed. Supplementation with AmO caused mild pro-oxidant activity resulting in improved uptake of oxidative destruction products and modulation of catalase and SOD activity with subsequent development of an antioxidant effect. These findings were very distinct in athletes but less pronounced in diabetics. Redistribution of haemoglobin ligands in athletes indicates involvement of haemoproteins in free radical reactions during AmO supplementation. Improvement in HRV by daily consumption of AmO as observed in both study groups suggested increased production of endogenous oxygen and enhancement of the cardio-respiratory function. The advantage of activation of aerobic metabolism in OS-related disorders resulting in improved self-organization of the living system and hormetic reaction mechanisms are discussed.

Interaction of C60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa cells

With an aim to elucidate the effects of C60 fullerene complexed with antibiotic doxorubicin (Dox) on model bilipid membranes (BLM), the investigation of the electrical properties of BLM under the action of Dox and C60 fullerene, and of their complex, C60+Dox,was performed. The complex as well as its components exert a clearly detectable influence on BLM, which is concentration-dependent and also depends on phospholipid composition. The mechanism of this effect originates either from intermolecular interaction of the drug with fatty-acid residues of phospholipids, or from membranotropic effects of the drug-induced lipid peroxidation, or from the sum of these two effects. By fluorescence microscopy the entering of C60 + Dox complex into HeLa cells was directly shown.

Comparative Analysis of the Antineoplastic Activity of C60 Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo

The antitumor activity of pristine C60 fullerene aqueous solution (C60FAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats. The number, size, and location of the tumors were measured, and the pathology was examined. It was found that the number of tumors and total lesion area decreased significantly under the action of C60FAS and MI-1. Because these drugs have different mechanisms of action, their simultaneous administration can potentially increase the effectiveness and significantly reduce the side effects of antitumor therapy.

Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate.

In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes.

Morphofunctional parameters of blood cells of a rat with 1,2-dimethylhydrazine-induced colon carcinogenesis

The reduction of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) whereas increasing of reticulocytes number and indirect bilirubin after 20 weeks of experiment of dimethylhydrazine (DMH)-induced colon carcinogenesis indicate the hemolysis of red blood cells due to the DMH influence during tumor development. The slight increasing of number of monocytes and platelets, as well as considerable increasing of a number of eosinophilic granulocytes, has been observed. Reduction of number of hemoglobin and erythrocytes, slight increase of number of monocytes, and significant increase in number of platelets in blood of rats follows 26 weeks of the experiment (after 6 weeks of DMH discontinuation). Anemia with thrombocytosis accompany cancer in humans and the model of DMH-induced colon cancer is appropriate not only for studies of carcinogenesis and searching of new antineoplastic drugs but also for the development of correctional approaches of cancer-associated changes in the hematopoietic system.

Effects of 5-Amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one Intake on Digestive System in a Rat Model of Colon Cancer

Introduction. Pyrrol derivate 5-amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one (D1) has shown antiproliferative activities in vitro, so investigation of the impact of D1 intake on gut organs in rats that experienced colon cancer seems to be necessary. Materials and Methods. D1 at the dose of 2.3 mg/kg was administered per os daily for 27 (from the 1st day of experiment) or 7 (from the 21st week of experiment) weeks to rats that experienced 1,2-dimethylhydrazine (DMH)-induced colon cancer for 20 weeks. 5-Fluorouracil (5FU) was chosen as reference drug and was administered intraperitoneally weekly for 7 weeks (from the 21st week of experiment) at the dose of 45 mg/kg. Results. Antitumor activity of D1 comparable with the 5FU one against DMH-induced colon cancer in rats was observed (decrease of tumor number and tumor total area up to 46%). D1 attenuated the inflammation of colon, gastric and jejunal mucosa, and the liver, caused by DMH, unlike 5FU, aggravating the latter. In addition, D1 partially normalized mucosa morphometric parameters suggesting its functional restore. Conclusions. D1 possesses, comparable with 5-fluorouracil antitumor efficacy, less damaging effects on the tissues beyond cancerous areas and contributes to partial morphological and functional gut organs recovery.

Effect of С60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats

The application of pristine С60 fullerene aqueous colloid solution (C60FAS; 0.5 mg/kg body weight) for rats experienced acute colitis, either intraperitoneally or intrarectally (1) restores the colonic mucosa healing and epithelial barrier integrity, evidenced by autopsies and histological findings and the normalization of phenolsufonphthalein dye daily excretion; (2) attenuates the consequences of hemorrhages, such as signs of anemia and increased platelet count; (3) improves the liver redox status suppressing the lipid peroxidation (malonic dialdehyde and protein carbonyl group levels tended down) and stimulating the antioxidant defense system (glutathione peroxidase activity grew up). In addition, C60FAS intrarectally increases the monocyte count and decreases content of neutrophil granulocytes, i.e. diminishes the rate of the inflammatory process and activates the processes of colon tissues restoring with monocytes involvement. Therefore, intrarectal administration of C60FAS may serve as an efficient tool of ulcerative colitis therapy.