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Biomedical subjects

W M Przybyszewski

Publications and source records attributed to W M Przybyszewski.

12 recordsLinked to original sources
PubMed1994

Early peroxidizing effects of myocardial damage in rats after gamma-irradiation and farmorubicin (4'-epidoxorubicin) treatment.

Changes in lipid peroxide levels (TBA-RS) in rat serum and heart tissue as well as creatine kinase enzyme (CPK) activity in serum were used as early indicators of peroxidizing effects of heart damage after fractionated gamma-irradiation (4 x 5 Gy) and/or farmorubicin (4 x 2.5 mg/kg) treatment. An increase in the TBA-RS and enzyme activity was observed after the action of both agents given separately or in combination. The maximal expression of biochemical effects appeared a few days after irradiation or farmorubicin treatment. The application of the antioxidant, vitamin E, diminished the level of TBA-RS in serum and in heart homogenates plus CPK activity in serum, indicating the involvement of peroxidizing mechanisms in myocardial damage by both agents.

Animals↗
PubMed1989

Hydroxyurea-induced toxic side-effects in animals and an attempt at reducing them with vitamins E and C.

Using the changes in several blood parameters and in the histological picture of the liver as markers of toxicity, the effect of hydroxyurea (HU) in healthy rabbits or mice was examined during two weeks after a single administration of this drug. In rabbits a transient significant decrease in blood erythrocyte count with a gradual increase in their osmotic resistance, a suppression of granulocyte phagocytic capacity, and an elevation of acid phosphatase activity in the serum were found. An increase in the proportion of lymphocytes without detectable lysosomes as tested by supravital staining also appeared. No significant difference was observed in the white cell count and lipoperoxide levels after HU administration. Histological picture of the liver, excised from HU-treated mice, indicated a marked hepatotoxicity of the drug. Some of the toxic effects were reduced in animals supplemented with vitamins E and C.

Acid Phosphatase↗
PubMed1987

Protection of L5178Y cells by vitamin E against acute hydroxyurea toxicity does not change the efficiency of ribonucleotide reductase-mediated hydroxyurea-induced cytotoxic events.

Exposure of L5178Y cells in culture to 0.2 mM hydroxyurea (HU) for up to 48 h induces inhibition of DNA synthesis, killing of about 20% of cells during the first 24 h exposure, gradual progress of cells into the state of unbalanced growth (measured as progressive increase in cell size, DNA protein ratio and acid phosphatase activity) with final death of the majority of cells. These effects were used to compare effectiveness of rapid and late HU cytotoxicity in cells treated with HU in the presence or absence of vitamin E, employed as a protective agent against non-specific toxicity of HU. It has been found that while the presence of vitamin E prevents cell killing induced by HU treatment during first 24 h, its presence does not change the progress of cells into the state of unbalanced growth and final cell killing. It is suggested that the protection exerted by vitamin E against HU-induced side toxicity does not change the effectiveness of ribonucleotide reductase-mediated DNA synthesis inhibition, leading to cell death through the state of unbalanced growth.

Animals↗
PubMed1986

Mechanism of unbalanced growth-induced cell damage. I. A probable role for hydrolytic enzymes synthesis.

This study examines the relationship between cell progress into the state of unbalanced growth, hydrolytic enzyme activities and cell survival during the exposure of L5178Y cells to hydroxyurea (HU), excess thymidine (dThR), hydroxyurea with excess of four deoxyribonucleosides (dNR) or excess dTHR with deoxycytidine (dCR). Cell progress into the state of unbalanced growth was measured as cell size, protein/DNA ratio and protein content per cell. Activities of two lysosomal (acid phosphatase, beta-N-acetylglucosaminidase) and one cytoplasmic non-lysosomal (LDH) enzymes were determined. It has been found that in cells arrested by HU or excess dThR, a progressive cell volume increase with protein/DNA imbalance is correlated with a progressive increase in lysosomal and non-lysosomal hydrolase activities in the cells and in the medium and with a marked lethal effect. Cell volume increase, enhancement of enzyme activities and cell killing could be prevented in HU-arrested cells by concomitant addition of excess dNR (deoxyadenosine, deoxyguanosine, thymidine, deoxycytidine) leading to equal inhibition of DNA and protein synthesis. Control-like values of all parameters were achieved also in cells in which the dThR-inhibiting effect was reversed by dCR addition. It is suggested that a common pathway in the mode of action of the chemotherapeutic agents inducing cell killing through the state of unbalanced growth can be the over-production, abnormal accumulation and progressive leakage of numerous hydrolytic enzymes through the cell membranes, leading in consequence to 'lytic' cell death.

Acetylglucosaminidase↗
PubMed1986

Effect of hydroxyurea treatment on lysosomal membrane stability and enzyme latency in L5178Y cells in culture.

The stability of lysosomes prepared from hydroxyurea (HU) treated or untreated L5178Y cells and exposed to an HU-free iso- or hypoosmotic solution was compared. The data revealed that exposure of the cells to 1-10 mM HU for few hours tends to stabilize lysosomes. Partial protection against this effect could be afforded by catalase and superoxide dismutase. Under the same conditions of HU treatment lysosomal enzyme latency remained similar in HU treated and untreated cells.

Acid Phosphatase↗
PubMed1985

Amelioration of hydroxyurea-induced suppression of phagocytosis in human granulocytes by free radical scavengers.

The exposure of human circulatory white cells in vitro to 0.1-1-10 mol/l hydroxyurea (HU) for 20 h induced a progressive dose-dependent suppression of the phagocytic activity of granulocytes. The suppressing effect of 20 h exposure to 1 mol/l HU was used to examine the protection afforded by free radical scavengers against HU-induced cytotoxicity. It has been found that, in the suitable concentration of the protecting agent, a substantial protective effect of sodium benzoate, acetylosalicylic acid, alpha-tocopherol, ascorbic acid, catalase, peroxidase or superoxide dismutase can be achieved.

Antioxidants↗
PubMed1984

Hydroxyurea has the capacity to induce damage to human erythrocytes which can be modified by radical scavengers.

The treatment of human erythrocytes with hydroxyurea [HU] results in the azide-dependent changes in osmotic fragility and in increased methemoglobin formation. Similar changes were induced by H2O2 treatment. However when H2O2 in the presence of azide stimulated malondialdehyde production, in the HU-treated cells no malondialdehyde was detectable. When subjected to an oxidant stress [sodium ascorbate] HU-treated erythrocytes were more fragile and revealed changes in the absorption spectrum of the TBA-reactive material in comparison with the cells treated with ascorbate alone. Partial protection by radical scavengers against certain HU-induced changes can be achieved. The results indicate that HU can damage erythrocytes and suggest the radical origin of these effects.

Ascorbic Acid↗
PubMed1983

Alteration in lysosome supravital staining as a marker of hydroxyurea-induced cytotoxicity and its modification by radical scavengers in L5178Y cells in culture.

Supravital staining of lysosomal membranes with euchrysine was employed to study hydroxyurea (HU)-induced side toxic effects in L5178Y lymphoblasts in culture. Exposure of cells to 0.1-1.0-10.0 mM HU-induced progressive increase in the proportion of cells without detectable lysosomal fluorescence. This effect preceded the occurrence of non-viable cells, determined by trypan-blue exclusion test. Addition of alpha-tocopherol, acetylsalicylic acid, sodium benzoate or ascorbic acid to the culture medium afforded a concentration-dependent modification of lysosomal response to HU treatment. It is suggested that the fluorescence technique of supravital lysosome staining can be a useful test in studies on the side toxic effects of free radical-forming drugs and their amelioration by radical scavengers.

Animals↗
PubMedDate not supplied

Protection against hydroxyurea-induced cytotoxic effects in L5178Y cells by free radical scavengers.

Exposure of L5178Y cells in culture to 1 mM hydroxyurea (HU) for 3 h followed by 24 h incubation in an HU-free medium induced an abnormal enlargement of about 40% of the cells in the population and post-treatment reduction of DNA synthesis in comparison with control cells. These effects were used to examine the protection afforded by free radical scavengers against HU-induced cytotoxicity. It has been found that with careful choice of conditions (suitable concentration of the protective agent, pretreatment of cells) substantial protective effect of alpha-tocopherol, sodium benzoate, acetylsalicylic acid, catalase, peroxidase or superoxide dismutase can be achieved.

Animals↗