Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice

Aim To investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphomabearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone. Methods The hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, De Ritis ratio, and coenzyme A fractions by McDougal assay. Glutathione level in animal tissues was measured with Ellman reagent, and the activity of glutathione reductase, transferase, and peroxidase was measured using standard biochemical assays. Results D-pantethine (500 mg/kg) and, to a lower extent, selenomethionine (600 μg/kg) partially reduced the negative side effects (leukocytopenia and erythropenia) of Dx (5 mg/kg) in NK/Ly lymphoma bearing animals on the 14th day of their treatment. This increased animal survival time from 47-48 to 60+ days and improved the quality of their life. This ability of D-pantethine and selenomethionine was realized via hepatoprotective and immunomodulating activities. D-pantethine also restored the levels of acid-soluble and free CoA in the liver of tumor-bearing animals, while selenomethionine caused the recovery of glutathione peroxidase levels in the liver, which was significantly diminished under Dx treatment. Both compounds decreased glutathione level in the liver, which was considerably induced by Dx. Conclusions Antioxidants selenomethionine and D-pantethine partially reversed the negative side effects of Dx in NK/Ly lymphoma-bearing mice and significantly increased the therapeutic efficiency of this drug in tumor treatment

Оценка селективности сорбентов для связывания IgG на основе трипептидных лигандов

Biospecific sorbents for the removal of IgG and subclasses from biological fluids based on oligopeptides, containing aromatic amino acid residues, were created. The selectivity properties of specific sorbents for IgM, IgE, and plasma proteins were evaluated. It was found that the created sorbents exhibit the low activity to the total plasma protein, albumin, IgM, IgE and are highly specific for IgG.Созданы биоспецифические сорбенты для удаления IgG и подклассов из биологических жидкостей на основе олигопептидов, содержащих остатки ароматических аминокислот. Проведена оценка селективности специфических сорбентов по отношению к IgM, IgE и белкам плазмы крови. Обнаружено, что созданные сорбенты прояв- ляют низкую активность к общему белку плазмы крови, альбумину, IgM, IgE и высоко специфичны к IgG

TO THE 250TH ANNIVERSARY OF ANDREI (JĘ Ę DRZEJ) Ę Ś NIADECKI – AN OUTSTANDING BIOLOGIST, CHEMIST, PHYSICIAN, TEACHER AND PUBLIC FIGURE

A brief review of the scientific activities of an outstanding biologist, chemist, physician and health care organizer, Professor of the Vilna University, Academician of the St. Petersburg Medical-Surgical Academy Andrei (Jędrzej) Śniadecki, whose life is closely connected with Grodno region. Numerous scientific events are devoted in 2018 to the memory of the founder of the theory of epigenesis, the Sniadecki heritage and the modern interpretation of the role of epigenesis in normal conditions and pathology

Antioxidant status and glutathione redox potential of erythrocytes in patients with acute coronary syndrome

Indicators of oxidative stress (OS), systemic inflammation, metabolism and redox status of glutathione (GSH) were investigated and compared in patients with ST-segment elevation myocardial infarction on electrocardiograms (STEMI), and patients with unstable angina (UA). The elevated and decreased myeloperoxidase level, superoxide dismutase activity, and moderate increased plasma levels­ of interleukin-6, while maintaining the antioxi­dant potential, were found in Group 1. Disor­ders in pro-/antioxidant balance and systemic inflammatory response were manifested in UA. Increased GSH concentration (and total GSH) in erythrocytes has been established for STEMI patients and the decreased GSH for UA patients. Thus, a significant shift of erythrocytes redox to oxidization and increase (unlike STEMI patients) of glutathione peroxidase activity were recorded. Mechanisms of the pro- and antioxidant functions of red blood cells in acute coronary syndrome are considered. The role of red blood cell glutathione to provide more oxidized intravascular environment for S-glutathionylation and optimization of redox signa­ling in target cells is pronounced

Antioxidants selenomethionine and D-pantethine differentially affect doxorubicin’s action on glutathione system in human leukemia cells varying in their resistance to chemotherapy in vitro

Rapid development of multiple drug resistance and occurrence of negative side effects in cancer patients arising at the treatment belong to the main problems in cancer chemotherapy. Recently, it was shown that specific antioxidants (selenomethionine – SeMet and D-pantethine – D-Pt) possessed nephro-, myelo- and hepatoprotective activity at doxorubicin’s (Dx) action in tumor-bearing mice. Besides, these antioxidants inhibited a cytotoxic action of Dx toward chemotherapy-sensitive tumor cells, and enhanced the cytotoxic effect of this drug toward selected drug-resistant tumor cell lines (e.g. HL-60/vinc, HL-60/adr), while in other such lines (e.g. HCT-116/Bax(−/−), HCT-116/p53), it was not effective. The aim of present study was to investigate the molecular mechanisms of the revealed difference in the action of SeMet and D-Pt toward cytotoxic effects of Dx in tumor cells varying in drug resistance. Human leukemia cells of HL-60/wt line and its drug-resistant sublines HL-60/adr (overexpression of MRP-1) and HL-60/vinc (overexpression of P-gp) were used in this study. Treatment of cells with Dx led to the versatile action of this drug on the level of glutathione in each of the studied cell line and sublines. HL-60/wt cells were characterized by 8-fold lower GSH level under Dx treatment compared to control, while in HL-60/vinc and HL-60/adr cells GSH level was increased 2.2- and 8.2-fold (compared to untreated cells), correspondingly. The use of doxorubicin also led to significant rearrangement of GSSG/GSH ratio in these cell lines, leading to 2-fold elevation of GSSG level HL-60/vinc cells, and 2.5-fold decrease of this index in HL-60/adr cells. We have shown that a combined effect of SeMet or D-Pt on the background of the cytotoxic action of doxorubicin on HL-60/vinc cells is accompanied by a 2-fold decrease in both oxidized and reduced glutathione levels. Such an effect of these antioxidants can serve as an explanation of their sensitizing effect on the cells of the HL-60/vinc subline under Dx’s action which we observed earlier. It should be noted that treatment with Dx led to a 2.5-fold increase in the activity of glutathione-S-transferase in the leukemia cells of HL-60/vinc subline. The antioxidants effectively reduced this indicator. SeMet and D-Pt differentialy affected the activity of glutathione-S-transferase in HL-60/adr cells. In conclusion, our data demonstrate an important role of the antioxidants on the functional state of the glutathione system in tumor cells that differ in their drug resistance. The obtained results suggest an important role of glutathione-S-transferase in modulation of cancer drug resistance that is caused by P-glycoprotein overexpression, but not by the overexpression of MRP-1 protein. Selenomethionine and D-pantethine effectively inhibit this enzyme, thus, sensitizing P-gp overexpressing cells towards the action of doxorubicin. This event is accompanied by further decrease in GSH and GSSG levels in these cells, thus sensitizing them to Dx action. Further studies of the molecular mechanisms underlying this phenomenon are in progress