Biomedical subjects

M Suwalsky

Publications and source records attributed to M Suwalsky.

At least 37 records · Page 2Linked to original sources

PubMed1999

The anticancer drug chlorambucil interacts with the human erythrocyte membrane and model phospholipid bilayers.

The plasma membrane has gained increasing attention as a possible target of antitumor drugs. It has been reported that they act as growth factor antagonists, growth factor receptor blockers, interfere with mitogenic signal transduction or exert direct cytotoxic effects. Chlorambucil (4-[p-(bis[2-chloroethyl]amino)phenyl]butyric acid) is an alkylating agent widely used in the treatment of chronic lymphocytic leukaemia. Contradictory reports have been published concerning its interaction with cell membranes. Whereas a decrease in the fluidity of Ehrlich ascite tumor cells has been adduced, no evidences were found that chlorambucil changes membrane lipid fluidity and alkylating agents had effects in these systems even at highly toxic concentrations. Our results showed that chlorambucil at a dose equivalent to its therapeutical concentration in the plasma (3.6 microM) caused the human erythrocyte membrane to develop cup-shaped forms (stomatocytes). Accordingly to the bilayer couple hypothesis, this means that the drug is inserted into the inner monolayer of the erythrocyte membrane, a conclusion supported by X-ray diffraction performed on multilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the erythrocyte membrane, respectively. It is concluded that the cytotoxic effect of chlorambucil might be due to alteration of the structure and therefore of the physiological properties of cell membranes such as fluidity, permeability, receptor and channel functions.

Adult↗

PubMed1998

Cu2+ ions interact with cell membranes.

The influence of Cu2+ ions on the physical properties of resealed human erythrocyte membranes was studied by fluorescence spectroscopy. A net ordering effect was observed at the hydrophobic-hydrophilic interface both in the bulk as well as in the lipid-protein boundary. The explanation for this result was found by X-ray diffraction performed in multilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. Cu2+ did not significantly affect the structure of DMPE; however, DMPC polar head and hydrocarbon chain arrangements were perturbed at low but reordered at high Cu2+ concentrations. These effects were respectively explained in terms of a limited and extended interaction between Cu2+ ions and DMPC PO4 groups. Thus, the ordering effect in the erythrocyte membrane could be based on the interaction of this cation with phosphatidylcholine phosphate groups located in its outer leaflet. This binding, besides producing a decrease of membrane fluidity, might also induce a change in its electric field. These two effects should affect the activity of membrane proteins, particularly of ion channels. In fact, it was found that increasing concentrations of Cu2+ ions applied to either the mucosal or serosal surface of the isolated toad skin elicited a dose-dependent decrease of the short-circuit current (SCC) and of the potential difference (PD). These results lead to the conclusion that Cu2+ ions inhibited Na+ transport across the epithelial cell membranes.

Animals↗

PubMed1998

The organochlorine herbicide chloridazon interacts with cell membranes.

Chloridazon is a widely used organochlorine herbicide. In order to evaluate its perturbing effect on cell membranes it was made to interact with human erythrocytes, frog adrenergic neuroepithelial synapse and molecular models. These consisted in multilayers of dimyristoylphosphatidylethanolamine (DMPE) and of dimyristoylphosphatidyltidylcholine (DMPC), representative of phospholipid classes located in the inner and outer monolayers of the erythrocyte membrane, respectively. X-ray diffraction showed that chloridazon interacted preferentially with DMPC multilayers. Scanning electron microscopy revealed that 0.1 mM chloridazon induced erythrocyte crenation. According to the bilayer couple hypothesis, this is due to the preferential insertion of chloridazon in the phosphatidylcholine-rich external moiety of the red cell membrane. Electrophysiological measurements showed that nerve stimulation was followed immediately by a transient increase in short-circuit current (SCC) and in the potential difference (PD) of the neuroepithelial synapse. Increasing concentrations of chloridazon caused a dose-dependent and reversible decrease of the responses of both parameters to 76% of their control values. The pesticide induced a similar (28%) significant time-dependent decrease in the basal values of the SCC and of PD. These results are in accordance with a perturbing effect of chloridazon on the phospholipid moiety of the nerve fibre membrane leading to interference with total ion transport across the nerve skin junction.

Animals↗

PubMed1997

The organochlorine pesticide heptachlor disrupts the structure of model and cell membranes.

Heptachlor is an organochlorine pesticide which is particularly toxic for aquatic life. A significant source of this pesticide for infants is breast milk, where its concentration is considerably higher than in dairy milk. Given the lipophilic character of heptachlor, lipid-rich cell membranes are a very plausible target for its interaction with living organisms. In order to evaluate its toxicity towards cell membranes, heptachlor was made to interact with human erythrocytes and molecular models of the red cell membrane. These consisted of multilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), which are types of phospholipids that are respectively located in the outer and inner monolayers of the erythrocyte membrane, and large unilamellar vesicles (LUV) of DMPC. Observations by scanning electron microscopy showed that 10 mM heptachlor produced various degrees of shape alterations to erythrocytes, which ranged from a few blebs in some cells to a great number of protuberances in others. On the other hand, experiments performed by X-ray diffraction on DMPC and DMPE indicated that the bilayer structure of DMPC was much more affected by heptachlor than that of DMPE. Measurements by fluorescence spectroscopy on DMPC LUV confirmed the X-ray diffraction results in that both the hydrocarbon chain and polar head regions of DMPC were structurally perturbed by heptachlor. The results obtained from the model studies could explain the shape changes induced to red cells by heptachlor. According to the bilayer hypothesis, they were due to the preferential interaction of heptachlor with the phosphatidylcholine-rich external moiety of the erythrocyte membrane. It is therefore concluded that toxic effects of this pesticide can be related to its capacity to perturb the phospholipid bilayer structure, whose integrity is essential for cell membrane functions.

Dimyristoylphosphatidylcholine↗

PubMed1996

Interaction of 2,4-dichlorophenoxyacetic acid (2,4-D) with cell and model membranes.

2,4-dichlorophenoxyacetic acid (2,4-D), a widely used herbicide, is a component of the "agent orange' whose toxicity has been extensively studied without definite conclusions. In order to evaluate its perturbing effect upon cell membranes, 2,4-D was made to interact with human erythrocytes and molecular models. These studies were performed by scanning electron microscopy on red cells, fluorescence spectroscopy on dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles and X-ray diffraction on multilayers of DMPC and dimyristoylphosphatidylethanolamine (DMPE). It was observed that 2,4-D induced a pronounced shape change to the erythrocytes. This effect is explained by the herbicide interaction with the outer monolayer of the red cell membrane.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1995

[Radiologic visibility of breast fibroadenomas].

From a clinical point of view, all mammary fibroadenomas are similar. However some of them are not visible in mammograms, phenomenon probably related to glandular density. Aiming to elucidate whether the lack of visibility is caused by the glandular density or by tumor itself, a three stage study was performed. In 201 cases the mammographic visibility of fibroadenomas was determined and correlated with patient's age, the presence of fibrocystic disease and tumor histological type; after surgical excision, 18 fibroadenomas were sliced into 5 mm thick samples and X rayed to determine their visibility; finally 2 visible and 2 non visible tumors were calcinated at 550 degrees C and their ashes subjected to X-ray diffraction analysis. Twenty two percent of fibroadenomas were not visible on mammography, this percentage was higher for intracanalicular tumors, in younger women and in the presence of fibrocystic disease. Sixteen percent of excised and sliced tumors were not visible on X rays. Also, differences were found in X-ray diffraction studies between visible and invisible tumors, probably related to NaCl and KCl tumor content.

Adolescent↗

PubMed1995

Morphological changes in human erythrocytes induced in vitro by antiarrhythmic drugs.

Several hypotheses suggest that the molecular mechanism of action of class I antiarrhythmic drugs (AAD) involve non-specific interactions of these compounds with phospholipid bilayers of the myocardial membrane that surround and functionally modulate ion transport by sodium channels. As a result of these interactions the channel function would be altered. To probe the validity of these hypotheses three AAD with different degrees of lipophilicity were made to interact in vitro with human erythrocytes in a wide range of concentrations. The most lipophilic drug was asocainol (ASOC), the least one was procainamide (PROC) while the lipophilicity of the third, quinidine (QUIN), lay somewhere between the other two. The observations made by scanning electron microscopy (SEM) showed that the three AAD produced profound shape alterations to the incubated erythrocytes. However, the type and intensity of these changes were dependent on the drug under study and its concentration.

Anti-Arrhythmia Agents↗

PubMed1994

Interaction of antiarrhythmic drugs with model membranes.

Several hypotheses link the molecular mechanism of action of the antiarrhythmic drugs (AAD) that belong to class I to nonspecific interactions with phospholipids sited in the neighborhood of the sodium channels in the membrane of the myocard. The interactions of asocainol (ASOC), procainamide (PROC) and quinidine (QUIN) with: (a) multibilayers of dimyristoylphosphatidylcholine (DMPC) and of dimyristoylphosphatidylethanolamine (DMPE), in both a hydrophobic and a hydrophilic medium, and (b) DMPC vesicles, were studied, respectively, by X-ray diffraction and fluorescence spectroscopy. It was found that the three AAD interacted with the lipid bilayers. However, the extension of these interactions depended on the nature and concentration of the lipids and AAD as well as on the medium where the interactions were performed. The different capacity of ASOC and PROC to perturb the bilayer structures, mainly that of DMPC, indicated that the interactions were strongly dependent on the lipophilicity of these drugs. The fact that QUIN did not completely interact in accordance to its lipophilicity suggested that other factors also play a role in these interactions. It is concluded that it may be valid the suggested molecular mechanisms of action of class I AAD involving their interaction with the membrane phospholipids.

Anti-Arrhythmia Agents↗

PubMed1992

Morphological changes on nerves and histopathological effects on liver and kidney of rats by pentachlorophenol (PCP).

1. The chronic toxicity of pentachlorophenol (PCP) was studied in rats after 90-120 days of oral administration ad libitum of 0.3-3 mM PCP aqueous solutions. 2. Morphological studies of their sciatic nerves were performed by optical and electron microscopy. 3. They showed degenerative changes in about 10% of the A and B type of nerve fibers. 4. The myelin sheath was discontinued by complete separation in several concentric rings while some other parts of the nerve exhibited a variable loss of neurotubules, neurofilaments and other axoplasmic components. 5. However, the C type of nerve fibers, the blood vessels and the perineurium did not show any morphologic alteration. 6. It was also found that in the liver PCP caused hemodynamic vein changes and injury in the hepatocytes such as cellular swelling and vacuolar degeneration. 7. The damage in the kidney occurred primarily in the glomeruli and secondarily in the proximal tubules causing turbid tumefaction and the formation of casts in the tubular lumen.

Animals↗

PubMed1977