Shape and volume changes in rat erythrocytes induced by surface-active alkyltrimethylammonium salts and sodium dodecyl sulphate

Isomaa, Boris; Paatero, Gun I.L.

doi:10.1016/0005-2736(81)90248-0

Cited by 20 publications

(7 citation statements)

References 22 publications

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“…Certain quaternary ammonium compounds have been shown to be effective in stopping parasite growth in vitro by inhibiting PC biosynthesis at very low ICst0s of 7 x 10-7, 10-6, and 4 x 10-6 M, respectively (2). In this study we show that a variation of the number of carbon atoms in the alkyltrimethylammonium alkyl chain results in an optimal antiplasmodial activity in dodecyltrimethylammonium, with an ICso of 5 x 10-7 M. The addition of lethal doses of DTMA, DM, or HC3 for pulse-inhibitory periods (12, 24, or 48 h) to a synchronous culture showed that DTMA only Quaternary ammonium compounds are reported to penetrate the erythrocyte membrane with difficulty, first getting into the outer leaflet of the lipid bilayer and then gradually translocating into the inner leaflet (11,12). Nevertheless, the antiplasmodial effect of these compounds is not linked to their detergent and hemolytic properties or to a mere alteration of host cell membranes, as reported previously (2).…”

Section: Resultsmentioning

confidence: 99%

Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport

Ancelin¹,

Vial²

1986

Antimicrob Agents Chemother

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Hemicholinium 3, decamethonium, and decyltrimethylammonium previously have been demonstrated to be efficient inhibitors, with 50% inhibitory concentrations of 4 x 10-6, 10-6, and 7 x 10-7 M, respectively. We show that lengthening of the alkyl chain of decyltrimethylammonium by successive additions of two carbon atoms up to hexadecyltrimethylammonium results in a very low 50% inhibitory concentration of 5 x 10-7 M for dodecyltrimethylammonium. Furthermore, hemicholinium 3 and decamethonium exerted their antiplasmodial activity, regardless of the developmental stage of the parasite, whereas decyltrimethylammonium was particularly lethal for the mature forms. After infected erythrocytes with radioactive choline were supplied, the determination of the water-soluble choline-containing compounds, as well as the assay of choline kinase activity, showed that the specific inhibition of phosphatidylcholine biosynthesis is related to the impairment of choline entry into erythrocytes. Thus, the impairment of the transport of choline, a natural polar head group of phospholipids, appears to be lethal for Plasmodium falciparum in vitro and could be a reasonable approach for a new malaria chemotherapy.The urgent need for new therapeutic approaches to Plasmodium falciparum malaria often has been pointed out (18) because of the resistance of both mosquitoes and parasites to various pesticides and conventional drugs (27). We have shown previously that phospholipid (PL) metabolism could constitute an ideal target for a new chemotherapy (25) because of its magnitude (9, 21, 24, 26) and specificity, because little or no PL biosynthesis occurs in mature mammalian erythrocytes (23). In our previous studies we showed that the lethal effect of quaternary ammonium compounds on P. falciparum in vitro involved the inhibition of phosphatidylcholine (PC) biosynthesis from choline, the natural polar head group of PC (2). Furthermore, we have shown that no alteration in the biosynthesis of the other PL, or of proteins or nucleic acids, occurred. In this study we establish that this inhibition of PC biosynthesis is due to an impairment of choline transport into infected erythrocytes. In addition, we show that the bis-onium compounds act regardless of the developmental stage of the parasite, whereas the monoammonium compound that was tested, decyltrimethylammonium, appears to be most lethal for the maturing parasites (i.e., the schizont form). Obtaining Plasmodium knowlesi-infected erythrocytes. Splenectomized Macaca fasciciilaris monkeys (weight, 3 to 6 kg; Sanofi, Montpellier, France), were infected with cryopreserved (20) P. knowlesi Washington, variant 1 (from G. Mitchell, Guy's Hospital, London). On days 6 to 9, highly infected blood cells were collected and then washed with basic medium (medium B: RPMI 1640 supplemented with 25 mM HEPES [pH 7.4] containing 40 ,uM choline and inositol and 140 FLM serine). Leukocytes were eliminated by passage through a cellulose powder column (CF 11; Whatman, Inc., Clifton, N.J.) (10). After two washes with ...

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Section: Resultsmentioning

confidence: 99%

Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport

Ancelin¹,

Vial²

1986

Antimicrob Agents Chemother

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“…It was shown that alkyl-trimethylammonium salts and SDS, which induce echinocytic shapes in rat RBCs, further inverted into discocytes and stomatocytes as the incubation proceeded, as the concentration increased, or upon cooling to room temperature. 54 It was also shown that RBCs exposed to dodecylzwittergent or SDS attained a stomatocytic shape when washed in a buffer containing bovine serum albumin. 55 According to the model of perforation by Cyt1Aa, the integrity of the cell membrane remains intact, but the flow of cations through the pores disturbs the osmotic balance of the cell.…”

Section: Relative Toxicities Of Cyt1aa and Cyt1camentioning

confidence: 98%

Cyt1Aa Toxin: Crystal Structure Reveals Implications for Its Membrane-Perforating Function

Cohen

Albeck

Ben‐Dov

et al. 2011

Journal of Molecular Biology

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“…Fiddler et al (4) observed morphologic changes of erythrocyte ghosts, made by several methods, to echinocytes or stomatocytes. In fact, simply washing erythrocytes can cause the cell shape to change to an echinocytic form, possibly because various plasma proteins are removed from the surface of the erythrocyte (20). These morphologic forms presumably are cleared by the reticuloendothelial system more rapidly than normal discoid erythrocytes.…”

Section: Resultsmentioning

confidence: 99%

Stability of erythrocyte ghosts: a gamma-ray perturbed angular correlation study.

Kruse¹,

Tin²,

Baldeschwieler³

1983

Proc. Natl. Acad. Sci. U.S.A.

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The structural integrityof erythrocyte ghosts made by the preswell and slow-dialysis techniques has been studied in vitro by use of y-ray perturbed angular correlation (PAC) techniques and also by standard in vitro leakage methods employing sequestered labeled markers. Complexes of "'In3+ and nitrilotriacetate were encapsulated in ghosts made from human, rabbit, rat, and mouse erythrocytes, and their leakage was monitored by both methods. In addition, "2'I-labeled bovine serum albumin was encapsulated, and ghost integrity was monitored by conventional leakage measurements. With the PAC technique the percentage of material released from human ghosts was determined quantitatively, and the results were equivalent to those obtained by the conventional method. In addition, at various times after intravenous injection, tissue distribution of the ghosts in the mouse was studied. The percent injected dose per gram of tissue of the labeled surface proteins of erythrocyte ghosts in circulation approximated that of the entrapped labeled albumin. This suggests that the ghost membrane and contents are strongly associated in viva Large "MI-labeled bovine serum albumin molecules and small "'1In3+-nitrilotriacetate complexes were delivered in high quantities to the lung initially, and to the liver and spleen. Because erythrocyte ghosts have the ability to entrap a wide range of substances and deliver them to specific organs, ghosts may be preferable to other drug carriers or drug therapy for treatment of certain disorders.An attractive strategy for the in vivo delivery of biologically active molecules is the encapsulation of drugs or enzymes in erythrocytes. As carriers, erythrocytes offer several advantages over other systems: they can entrap large volumes of concentrated loading material, and they can avoid host immunologic reactions if they are from isologous or autologous blood. Different enzymes and drugs have been successfully encapsulated by erythrocytes and delivered to specific cell and tissue sites in animal models (1-3). Methods of entrapment, such as the preswell, rapid-lysis, and slow-dialysis methods, involve variations of erythrocyte osmotic lysing and resealing (4, 5); methods such as applying an external pulsed electric field or drug treatment induce membrane permeability changes or endocytic activity in erythrocytes (1,4,6). The successful entrapment of various active enzymes, transport systems, and drugs has been demonstrated (1-9). To develop theerythrocyte ghosts as practical carrier systems, we have studied the leakage of entrapped substances from ghosts of different species prepared by various methods, and we have studied the fate of the erythrocyte ghosts after administration in vivo.

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Shape and volume changes in rat erythrocytes induced by surface-active alkyltrimethylammonium salts and sodium dodecyl sulphate

Cited by 20 publications

References 22 publications

Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport

Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport

Cyt1Aa Toxin: Crystal Structure Reveals Implications for Its Membrane-Perforating Function

Stability of erythrocyte ghosts: a gamma-ray perturbed angular correlation study.

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