Biomedical subjects

Zofia Jóźwiak

Publications and source records attributed to Zofia Jóźwiak.

9 recordsLinked to original sources

PubMed2006

Combined effect of low-power laser irradiation and anthraquinone anticancer drug aclarubicin on survival of immortalized cells: Comparison with mitoxantrone.

The photodynamic response of the anthraquinone anticancer drug aclarubicin (ACL) was investigated in vitro and compared with that of mitoxantrone (MTX). Cultured immortalized rodent B14 and NIH 3T3 cells were used in the experiments as a model for cells with neoplastic phenotype. Long-term cytotoxicity and inhibition of cell proliferation assayed by the clonal growth and MTT-tetrazolium methods were estimated to compare the efficacy of aclarubicin and mitoxantrone in photosensitizing cells and their death after non-thermal exposure to monochromatic laser light. Green He-Ne (543.5 nm) or red semiconductor (670 nm) low-power laser (LPL) irradiations were applied. Different dose-responses of both cell lines to aclarubicin and mitoxantrone were found so that the cytotoxicity of MTX was considerably greater than the cytotoxicity of ACL. Phototherapy response (P < 0.0001) was observed only for B14 cells after sensitisation with aclarubicin. Under the same conditions no significant effect of red light irradiation (semiconductor 670 nm laser) on survival of both cell lines treated with mitoxantrone was found.

Aclarubicin↗

PubMed2006

[Transferrin conjugates in the anticancer therapy].

To enhance the therapeutic efficiacy of anticancer drugs and reducing its systemic side-effects carriers are used. Transferrin is one of the very promising protein which can be used to transport drugs, DNA and ions into the cancer cells. Because of the fact that neoplastic cells have increased number of transferrin receptors, the transferrin can deliver the drugs directly to the neoplastic cells without injury of normal cells.

Animals↗

PubMed2005

Interaction of doxorubicin and idarubicin with red blood cells from acute myeloid leukaemia patients.

Doxorubicin (DOX) and idarubicin (IDA) are anthracycline antibiotics, widely used in human cancer treatment. The present study addressed the effects of these two drugs on lipid bilayer fluidity, protein conformation and microviscosity in erythrocytes from acute myeloid leukaemia patients, using electron spin resonance (ESR) spectroscopy and fluorescence measurements. Only DOX caused statistically significant changes in the parameters examined. Within 30 min of drug injection, changes were observed in the fluidity of the hydrophobic parts of the lipid bilayer and erythrocyte membrane protein conformation. These changes persisted for up to 24h. Analysis of the EPR Tempamine spectrum also showed that the microviscosity of the erythrocyte interior increased during the early stages of the drug effect. Idarubicin, in contrast, caused no identifiable change in any of the parameters studied and therefore seems to be safe for erythrocytes. We conclude that IDA is markedly less toxic than DOX to erythrocytes from acute myeloid leukaemia patients.

Adult↗

PubMed2003

Relevance of drug uptake, cellular distribution and cell membrane fluidity to the enhanced sensitivity of Down's syndrome fibroblasts to anticancer antibiotic-mitoxantrone.

Sensitivity of human fibroblasts derived from Down's syndrome (DS) individuals (S-240, T-158, T-74, T-164) and normal donors (S-126, WA-1) to anticancer antibiotic-mitoxantrone (1,4-dihydroxy-5,8-bis((2-((2-hydroxy-ethyl)amino)ethyl)amino)-9,10-anthracenedione dihydrochloride; MIT) and its relationship to the transport rate, cellular distribution and interaction with cell membrane were studied. The survival assay showed that MIT was more toxic to trisomic fibroblast lines than to normal cells. Studies of transport kinetics indicated that the amount of drug taken up and extruded by DS cells was diminished, compared to control cells. In contrast, the cellular level of MIT associated with DNA was greater in trisomic than in normal cells. The fluorescence anisotropy measurements of TMA-DPH and 12-AS demonstrated that the fluidity of the polar region of the outer lipid monolayer of DS cell membrane was decreased in comparison with normal cells. MIT treatment decreased fluidity of the inner hydrophobic region of plasma membrane, but only slightly influenced the fluidity of the outer surface of the cell membrane. Finally, we concluded that lowered membrane fluidity, diminished amount of MIT extruded by cells and the enhanced level of the drug associated with DNA could be responsible for the enhanced sensitivity of DS fibroblasts to the MIT treatment.

Antibiotics, Antineoplastic↗

PubMed2003

Evaluation of hydralazine and procainamide effects on fibroblast membrane fluidity.

In this study the membrane fluidity of fibroblasts under different pharmacological treatment was investigated. Two drugs, hydralazine and procainamide, were used to treat the immortalized mouse NIH 3T3 and hamster B14 fibroblasts. Membrane lipid dynamics was measured by fluorescence spectroscopy and electron spin resonance techniques. Two kinds of fluorescent probes (TMA-DPH and 12-(9-anthroyloxy)-stearic acid (12-AS)) and two spin labels (5-doxylstearic acid (5-DS) and 12-doxylstearic acid (12-DS)) were used to monitor fluidity in the upper polar and in the hydrophobic core regions of the lipid bilayer. The drugs influenced the membrane hydrophobic core, of which hydralazine induced fluidization and procainamide increased the rigidity. The membrane fluidity at the surface of the lipid bilayer was not modified by the drugs which indicates that both drugs intercalated mainly into the inner core of the cell membrane.

Animals↗

PubMed2003

Morphological and biochemical changes in human fibroblast lines induced by anthracyclines during apoptosis.

We show that treating human trisomic fibroblasts with anthracyclines - aclarubicin, daunorubicin and idarubicin - leads to certain changes in these cells; namely the activation of caspase 3, morphological changes and an increase in the level of intracellular calcium. These results suggest that anthracycline drugs are also able to induce apoptosis in pathological, trisomic cells.

Aclarubicin↗

PubMed2003

The nitroxides pirolin and pirolid protect the plasma membranes of rat cardiomyocytes against damage induced by anthracyclines.

This study was performed to evaluate the protective effects of pyrroline and pyrrolidine nitroxides Pirolin, PL, and Pirolid, PD, on the plasma membranes of rat cardiomyocytes treated in vitro with anthracycline drugs aclarubicin (ACL) and doxorubicin (DOX). The influence of two concentrations of drugs (10 and 20 microM) and nitroxides (0.1 and 1 mM) as well as their combinations (a drug and a nitroxide) on membrane fluidity was investigated. The plasma membranes of cardiomyocytes were labelled with a hydrophobic fluorescence probe 12-AS and membrane fluidity was estimated on the basis of the fluorescence anisotropy of the probe. We found that aclarubicin and doxorubicin induced a significant dose-dependent decrease in membrane fluidity, whereas the nitroxides (PL and PD) caused its increase. Preincubation of cardiomyocytes with Pirolin entirely protected plasma membranes of these cells against damage caused by DOX. In the same conditions no protective effect of Pirolid was observed. What is more, Pirolid in combination with DOX caused fluidisation of the plasma membranes of cardiomyocytes. Both nitroxides at low concentration (0.1 mM) protected plasma membranes against rigidification induced by aclarubicin, while high concentration (1 mM) was ineffective and caused fluidisation of the plasma membranes of cardiomyocytes.

Aclarubicin↗

PubMed2003

Effects of pyrroline and pyrrolidine nitroxides on lipid peroxidation in heart tissue of rats treated with doxorubicin.

Protection from doxorubicin-induced lipid peroxidation in vivo by two pyrroline and pyrrolidine nitroxides, Pirolin, PL, and Pirolid, PD, was examined in the heart tissue of rats treated with this drug. The level of lipid peroxidation was estimated on the basis of MDA content. A considerable (three-fold) increase in the MDA amount was found in heart homogenates from rats injected with doxorubicin, whereas no significant changes in MDA content compared to control were observed in cardiomyocytes treated with the nitroxides (Pirolin or Pirolid) only. Pirolin injected simultaneously with doxorubicin showed antioxidative effect and markedly attenuated lipid peroxidation in the heart tissue caused by this drug. In contrast to Pirolin, structurally related Pirolid was ineffective in the protection of heart myocytes from DOX-induced lipid peroxidation.

Animals↗

PubMed2003

Changes in GSH-antioxidant system induced by daunorubicin in human normal and diabetic fibroblasts.

We investigated the effect of daunorubicin on glutathione content and activity of GSH-related enzymes in cultured normal and diabetic human fibroblasts. Cells were incubated with 4 microM daunorubicin (DNR) for 2 h followed by culture in drug-free medium for up to 72 h. Treatment of diabetic cells with the drug caused a time-dependent depletion of intracellular GSH and a decrease of the GSH to total glutathione ratio. GSH depletion was accompanied by apoptotic changes in morphology of the nucleus. Analysis of GSH-related enzymes showed a significant increase of the activities of Se-dependent and Se-independent peroxidases and glutathione S-transferase. In contrast, glutathione reductase activity was reduced by 50%. Significant differences between normal and diabetic cells exposed to DNR were observed in the level of GST and Se-dependent glutathione peroxidase activities. These findings indicated that daunorubicin efficiently affects the GSH antioxidant defense system both in normal and diabetic fibroblasts leading to disturbances in glutathione content as well as in the activity of GSH-related enzymes.

Antibiotics, Antineoplastic↗