[en] Aminoglycoside antibiotics are hydrophilic molecules consisting of an animated cyclitol associated with amino sugar. They bind in vivo as well as in vitro to negatively charged membranes. Their use as chemotherapeutic agents is unfortunately accompanied by oto- and nephrotoxic reactions, and the purpose of this review is to examine the role of the molecular interactions between aminoglycosides and membranes in the development of nephrotoxicity. 31P Nuclear magnetic resonance (NMR) and fluorescence depolarization have been used to characterize the effect of aminoglycosides on phosphate heads and fatty acyl chains of phospholipids. 15N NMR has been used to obtain interesting information on regioselective interactions of amino groups of antibiotics with phospholipids. The binding of aminoglycosides with negatively charged membranes is associated with impairment of phospholipid catabolism, change in membrane permeability, and membrane aggregation. Biochemical analysis and 1H NMR spectroscopy have brought information on the molecular mechanism involved in the impairment of phospholipid catabolism. Nephrotoxic aminoglycosides could induce sequestration of phosphatidylinositol and therefore reduce the amount of negative charge available for optimal lysosomal phospholipase activity toward phosphatidylcholine included in liposomes that also contain cholesterol and sphingomyelin. Conformational analysis shows that aminoglycosides, which have a high potency to inhibit lysosomal phospholipase activity, adopt an orientation parallel to the lipid/water interface. This orientation of the aminoglycoside molecule at the interface is also critical to explain the marked increase of membrane permeability induced by less nephrotoxic aminoglycosides such as isepamicin and amikacin. This effect is indeed only observed with aminoglycosides oriented perpendicular to this interface, probably related to the creation of a local condition of disorder. The impairment of phospholipid catabolism, which is considered to be an early and significant step in the development of aminoglycoside toxicity, is therefore not related to the change in membrane permeability. However, the role of this latter phenomenon and of membrane aggregation for aminoglycoside nephrotoxicity could be further investigated.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Mingeot-Leclercq, M P; Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Brussels, Belgium
Brasseur, Robert ; Université de Liège - ULiège > Département GxABT > Chemistry for Sustainable Food and Environmental Systems (CSFES)
Schanck, A; Laboratoire de Chimie-Physique et de Cristallographie and Research Center for Advanced Materials, Louvain-La-Neuve, Belgium
Language :
English
Title :
Molecular parameters involved in aminoglycoside nephrotoxicity.
We gratefully acknowledge the help of Dr. P. M. Tulkens for helpful suggestions, critical reading, and encouragement. Drs. M.-B. Carlier and G. Laurent initiated the biochemical work, and L. Depienne and F. Van Bambeke performed some of the permeability studies. We are also indebted to ). P. Dieu, B. Van Loo, Drs. V. Cabiaux, D. Carrier, M. Deleers, P. Cailly, H. C. Jarell, C. Moussebois, and I. C. P. Smith, and to Professors V. Préat, M.-F. Ronveaux-Dupal, and M. Rosseneu for their collaborations and suggestions. We thank Belphar (Brussels), Bristol Benelux (Brussels), Bristol Laboratories (Syracuse, N.Y.), Continental Pharma (Brussels), Schering-Plough (Brussels), Kyowa Hakko Kogyo (Tokyo), Meiji Seika Kaisha (Tokyo), and Toyo Jozo (Shisuoka) for the generous gifts of the compounds. Studies in our laboratories received support from the Fonds National de la Recherche Scientifique (grant 1.5213.87), the Fonds de la Recherche Scientifique Médicale (grant 3.4553.88), the Programme visant à renforcer le Potentiel Scientifique dans les Technologies Nouvelles (PREST), the Belgian State-Prime Minister's Office of Science Policy Programming (Interuniversity Attraction Poles, grant 7bis and grants 82/87-39 and 88/93-122) and the Fonds du Développement Scientifique of the Université Catholique de Louvain. M.-P. Mingeot-Leclercq is Chercheur Qualifié and R. Brasseur is Maître de Recherches of the Belgian Fonds National de la Recherche Scientifique.
Alexander, A. M., Gonda, I., Harpur, E. S., and Kayes, J. B. 1979. Interaction of aminoglycoside antibiotics with phospholipid liposomes studies by microelectrophoresis. J. Antibiot. (Tokyo) 32:504-510.
Allen, T. M., and Cleland, L. G. 1980. Serum-induced leakage of liposome contents. Biochim. Biophys. Acta 597:418-426.
Aramaki, Y., and Tsuchiya, S. 1989. Interactions between aminoglycosides and phospholipids using liposomes: A possible mechanism of nephrotoxicity. Pharmacol. Res. 6:362-366.
Aubert-Tulkens, G., Van Hoof, F., and Tulkens, P. 1979. Gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts. Lab. Invest. 40:481-493.
Auslander, D. E., Felmeister, A., and Sciarrone, B. J. 1975. Drug-biomolecule interactions: Interaction of gentamicin with lipid monomolecular films. J. Pharm. Sci. 64:516-519.
Bachmann, L, and Schmitt, W. W. 1971. Improved cryofixation applicable to freeze etching. Proc. Natl Acad. Sci. USA 68:2149-2152.
Batenburg, A. M., Bougis, P. E., Rochat, H., Verkleij, A. J., and de Kruijff, B. 1985. Penetration of a car- diotoxin into cardiolipin model membranes and its implications on lipid organization. Biochemistry 24:7101-7110.
Batenburg, A. M., Von Esch, J. H., Leunissen-Bijvelt, A. J., Verkleij, A. J., and de Kruijff, B. 1987. Interaction of mellitin with negatively-charged phospholipids: Consequences for lipid organization. FEBS Lett. 223:148-154.
Beauchamp, D., Laurent, G., Maldague, P., and Tulkens, P. M. 1986. Reduction of gentamicin nephrotoxicity by the concomitant administration of poly-L-aspartic acid and poly-L-asparagine in rats. Arch. Toxicol. Suppl. 9:306-309.
Beauchamp, D., Laurent, G., Maldague, P., Abid, S., Kishore, B. K., and Tulkens, P. M. 1990. Protection against gentamicin-induced early renal alterations (phospholipidosis, increased DNA synthesis) by co-administration of poly-L-aspartic acid. J. Pharmacol. Exp. Eher. 255:858-866.
Benameur, H., De Gand, G., Brasseur, R., Van Vooren, J. P., and Legros, F. J. 1993. Liposomes-incor- porated dexamethasone palmitate: Chemical and physical properties. Int. J. Pharm. 89:157-167.
Berden, J. A., Barker, R. W., and Radda, G. K. 1975. NMR studies on phospholipid bilayers. Some factors affecting lipid distribution. Biochim. Biophys. Acta 375:186-208.
Borchardt, K., Heber, D., Klingmuller, M., Mohr, K., and Muller, B. 1991. The ability of cationic amphiphilic compounds to depress the transition temperature of dipalmitoylphosphatidic acid liposomes depends on the spatial arrangement of the lipophilic moiety. Biochem. Pharmacol. 42:561565.
Brasseur, R. 1988. Calculation of the three-dimensional structure of Saccharomyces cerevisiae cytochrome b inserted in a lipid matrix. J. Biol. Chem. 263:12571-12575.
Brasseur, R. 1990. TAMMO: Theoretical analysis of membrane molecular organization. In Molecular description of biological membrane components by computer-aided conformational analysis, vol. 1/1.A.6, ed. R. Brasseur, pp. 203-219. Boca Raton, Fla.: CRC Press.
Brasseur, R. 1991. Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations. J. Biol. Chem. 266:16120-16127.
Brasseur, R., Deleers, M., Malaisse, W. J., and Ruysschaert, J. M. 1982. Conformational analysis of the calcium-A23187 complex at a lipid-water interface. Proc. Natl Acad. Sci. USA 79:2895-2897.
Brasseur, R., Vandenbosch, C., Van Den Bossche, H., and Ruysschaert, J. M. 1983. Mode of insertion of miconazole, ketoconazole and deacylated ketoconazole in lipid layers. A conformational analysis. Biochem. Pharmacol. 32:2175-2180.
Brasseur, R., Laurent, G., Ruysschaert, J. M., and Tulkens, P. 1984. Interactions of aminoglycoside antibiotics with negatively-charged lipid layers. Biochemical and conformational studies. Biochem. Pharmacol. 33:629-637.
Brasseur, R., Carlier, M. B., Laurent, G., Claes, P. J., Vanderhaeghe, H. J., Tulkens, P. M., and Ruysschaert, j. M. 1985a. Interactions of.streptomycin and streptomycylamine derivatives with negatively charged lipid layers: Correlation between binding, conformation of complexes and inhibition of phospholipase activities. Biochem. Pharmacol. 34:1035-1047.
Brasseur, R., Chatelain, P., Goormaghtigh, E., and Ruysschaert, J. M. 1985b. Interactions of N-alkanols with dipalmitoylphosphatidylcholine: A semi-empirical conformational analysis. Biochim. Biophys. Acta 814:227-236.
Brasseur, R., Ruysschaert, J. M., and Chatelain, P. 1985c. Semi-empirical conformational analysis of propanolol interacting with dipalmitoylphosphatidylcholine. Biochim. Biophys. Acta 815:341-350.
Brasseur, R., Cabiaux, V., Falmagne, P. and Ruysschaert, J. M. 1986. pH Dependent insertion of a diphteria toxin B fragment peptide into the lipid membrane: A conformational analysis. Biochem. Biophys. Res. Commun. 136:160-168.
Brasseur, R., Killian, j. A., De Kruijff, B., and Ruysschaert, J. M. 1987. Conformational analysis of gramicidin-gramicidin interactions at the air water interface suggests that gramicidin aggregates into tubelike structures similar as found in the gramicidin-induced hexagonal H„ phase. Biochim. Biophys. Acta 903:11-17.
Brasseur, R., Cornet, B., Burny, A., Vandenbranden, M., and Ruysschaert, J. M. 1988. Mode of insertion into lipid membrane of the N-terminus HIV gp 41 peptide segment. AIDS Res. Hum. Retrov. 4:83-90.
Brasseur, R., Vandenbranden, M., Cornet, B., Burny, A., and Ruysschaert, J. M. 1990. Orientation into the lipid bilayer of an asymmetric amphipathic helical peptide located at the N-terminus of viral fusion proteins. Biochim. Biophys. Acta 1029:267-273.
Brasseur, R., Lins, L., Vanloo, B., Ruysschaert, J. M., and Rosseneu, M. 1992. Molecular modelling of the amphipathic helices of the plasma apolipoproteins. Proteins 13:246-257.
Carlier, M. B., Laurent, G., Claes, P. j., Vanderhaeghe, H. J., and Tulkens, P. M. 1983. Inhibition of lysosomal phospholipases by aminoglycoside antibiotics: Comparative studies in vitro. Antimicrob. Agents Chemother. 23:440-449.
Carlier, M. B., Brasseur, R., Laurent, G., Mingeot-Leclercq, M. P., Ruysschaert, J. M., and Tulkens, P. M. 1986. Use of an in vitro model to assess aminoglycoside-phospholipid interactions in relation with their nephrotoxicity. Food Chem. Toxicol. 24:815-816.
Carlier, M. B., Laurent, G., and Tulkens, P. M. 1987. Reduction of aminoglycoside-induced renal alterations in rats by co-administration of piperacillin at clinically relevant doses. 15th Int. Congr. Chemotherapy, Istanbul, Turkey, abstr. 883.
Carlier, M. B., Brasseur, R., Ruysschaert, J. M., and Tulkens, P. M. 1988. In vitro study and conformational analysis of 1 -N-aminohydroxybutyryl derivatives of aminoglycosides in correlation with their inhibitory potency towards lysosomal phospholipases. Arch. Toxicol. Suppl. 12:186-189.
Carrier, D., and Pezolet, M. 1986. Investigation of polylysine-dipalmitoylphosphatidylglycerol. Interactions in model membranes. Biochemistry 25:4167-4174.
Carruthers, A., and Melchior, D. L. 1983. Studies of the relationship between bilayer water permeability and bilayer physical state. Biochemistry 22:5797-5807.
Cater, B. R., Chapman, D., Hawes, S. M., and Saville, J. 1974. Lipid phase transitions and drug interactions. Biochim. Biophys. Acta 363:54-69.
Châtelain, and Brasseur, R. 1990. Conformational analysis of cardiovascular drug-lipid interactions: Propanolol and amiodarone. In Molecular description of biological membranes by computer aided conformational analysis, ed. R. Brasseur, pp. 43-62. Boca Raton, Fla.: CRC Press.
Chung, L., Kaloyanides, G., McDaniel, R., McLaughin, A., and McLaughin, S. 1985. Interaction of gentamicin and spermine with bilayer membranes containing negatively-charged phospholipids. Biochemistry 24:442-452.
Craig, W. A., Leggett, J., Totsuka, K., and Vogelman, B. 1988. Key pharmacokinetic parameters of antibiotic efficacy in experimental animal infections. J. Drug. Dev. 1 (Suppl. 3):7-15.
Cullis, P. R., and De Kruijff, B. 1976.31P-NMR studies of unsonicated aqueous dispersion of neutral and acidic phospholipids. Effects of phase transitions, p2H and divalent cations on the motion in the phosphate region of the polar head group. Biochim. Biophys. Acta 436:523-540.
Cullis, P. R., and de Kruijff, B. 1978a. Polymorphic phase behaviour of lipid mixtures as detected by 3,P NMR. Evidence that cholesterol may destabilize bilayer structure in membrane systems containing phosphatidylethanolamine. Biochim. Biophys. Acta 507:207-218.
Cullis, P. R., and De Kruijff, B. 1978b. The polymorphic phase behaviour of phosphatidylethalonamines of natural and synthetic origin. A 3’P NMR study. Biochim. Biophys. Acta 513:31-42.
Cullis, P. R., Verkleij, A. J., and Ververgaert, P. H. J. 1978. Polymorphic phase behaviour of cardiolipin as detected by 31P NMR and freeze-fracture techniques. Effects of calcium, dibucaine and chlorpro-mazine. Biochim. Biophys. Acta 513:11-20.
Cullis, P. R., de Kruijff, B., Hope, M. J., Verkleij, A. J., Nayar, R., Farren, S., and Bally, M. B. 1983. Structural properties of lipids and their functional roles in biological membranes. In Membrane fluidity in biology, vol. 1, ed. R. C. Aloia, pp. 39-81. New York: Academic Press.
Cuppage, F. E., Setter, K., Sullivan, P., Reitzes, E. J., and Melnykovych, A. O. 1977. Gentamicin nephrotoxicity. II. Physiological, biochemical and morphological effects of prolonged administration to rats. Virchows Arch. B 24:121-138.
Curtis, M. T., Gilfor, D., and Farber, J. L. 1984. Lipid peroxydation increases the molecular order of microsomal membranes. Arch. Biochem. Biophys. 235:644-649.
De Broe, M. E., Paulus, G. J., Verpooten, G. A., Roels, F., Buyssens, N., Wedeen, R., and Tulkens, P. M. 1984. Early effects of gentamicin, tobramycin and amikacin on the human kidney. Kidney Int. 25:643-652.
de Duve, C., and Wattiaux, R. 1966. Functions of lysosomes. Annu. Rev. Physiol. 28:435-492.
De Kruijff, B., Cullis, P. R., and Radda, G. K. 1975. Differential scanning calorimetry and 3’P NMR studies on sonicated and unsonicated phosphatidylcholine liposomes. Biochim. Biophys. Acta 406:620.
Deleers, M., and Brasseur, R. 1990. Transformation of ionophores at the lipid/water interface. In Molecular description of biological membranes by computer aided conformational analysis. Part 2. Mode of insertion of amphiphilic components into the lipid membrane, ed. R. Brasseur, pp. 17-26. Boca Raton, Fla.: CRC Press.
Deleers, M., Ruysschaert, J. M., and Brasseur, R. 1990. Molecular conformations of phorbol esters in a simulated lipid/water interface. In Molecular description of biological membranes by computer aided conformational analysis. Part I. Lipids structures and organizations, ed. R. Brasseur, pp. 221-230. Boca Raton, Fla.: CRC Press.
Di Virgilio, F., Steinberg, T. H., Swanson, J. A., and Silverstein, S. C. 1988. Fura-2 secretion and sequestration in macrophages. A blocker or organic anion transport reveals that these processes occur via a membrane transport system for organic anion. J. Immunol. 140:915-920.
Ellens, H., Siegel, D. P., Alford, D., Yeagle, P. L., Boni, L., Lis, L. J., and Bentz, J. 1989. Membrane fusion and inverted phases. Biochemistry 28:3692-3703.
Epand, R. M. 1990. Relationship of phospholipid hexagonal phases to biological phenomena. Biochem. Cell Biol. 68:17-23.
Epand, R. M., Epand, R. F., and McKenzie, R. C. 1987. Effects of viral chemotherapeutic agents on membrane properties. J. Biol. Chem. 262:1526-1529.
Esko, J. D., and Raetz, C. R. H. 1983. Synthesis of phospholipids in animal cells. In The enzymes-Lipid enzymology, vol. 16, ed. P. D. Bayer, pp. 208-253. New York: Academic Press.
Galla, H. J., and Sackmann, E. 1975. Chemically-induced lipid phase separation in model membranes containing charged lipids: A spin label study. Biochim. Biophys. Acta 301:509-529.
Ganesan, M. G., Weiner, N. D., and Schacht, J. 1983. Effects of calcium and neomycin on phase behavior of phospholipid bilayers. J. Pharm. Sci. 72:1465-1467.
Gilbert, D. N., Woods, C. A., Kohlhepp, S. J., Kohnen, P. W., Houghton, D. C., Finkbeiner, H. C., and Bennett, W. M. 1989. Polyaspartic acid prevents experimental aminoglycoside nephrotoxicity. J. Infect. Dis. 159:945-953.
Girke, S., Mohr, K., and Schrape, S. 1989. Comparison between the activities of cationic amphiphilic drugs to affect phospholipid-membranes and to depress cardiac function. Biochem. Pharmacol. 38:2487-2496.
Girotti, A. W., and Thomas, J. P. 1984. Damaging effects of oxygen radicals on resealed erythrocyte ghosts. J. Biol. Chem. 259:1744-1752.
Giurgea-Marion, L., and Tulkens, P. M. 1986. Effect of hydroxylation of the 2’,6’ diaminohexose moiety on the intrarenal accumulation of aminoglycoside antibiotics: Comparison between kanamycin B, tobramycin, dibekacin and gentamicin. In Recent advances in chemotherapy, ed. J. Ishigami, pp. 2679-2680. Tokyo: University of Tokyo Press.
Giurgea-Marion, L., Toubeau, G., Laurent, G., Heuson-Stiennon, J., and Tulkens, P. M. 1986. Impairment of lysosome-pinocytic vesicle fusion in rat kidney proximal tubules after treatment with gentamicin at low doses. Toxicol. Appl. Pharm. 86:271-285.
Goormaghtigh, E., Brasseur, R., and Ruysschaert, J. M. 1982. Adriamycin inactivates cytochrome c-oxi- dase by exclusion of the enzyme from its cardiolipin essential environment. Biochem. Biophys. Res. Commun. 104:314-320.
Goormaghtigh, E., Huart, P., Praet, M., Brasseur, R., and Ruysschaert, J. M. 1990. Adriamycin-mito- chondrial membrane interactions and cardiotoxicity. In Molecular description of membranes by computer aided conformational analysis. Part 2. Mode of insertion of amphiphilic components into the lipid membrane, ed. R. Brasseur, pp. 95-112. Boca Raton, Fla.: CRC Press.
Grynkiewicz, G., Poenie, M., and Tsien, R. Y. 1985. A new generation of Ca2’ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260(61):3440-3450.
Hanpft, R., and Mohr, K. 1985. Influence of cationic amphiphilic drug on the phase-transition temperature of phospholipids with different polar headgroups. Biochim. Biophys. Acta 814:156-162.
Hartmann, W., Galla, H. J., and Sackmann, E. 1977. Direct evidence of charge induced lipid domain structure in model membranes. FEBS Lett. 78:169-172.
Haydon, D. A., and Elliott, J. R. 1986. Surface potential changes in lipid monolayers and the “cut-off” in anaesthetic effects of N-alkanols. Biochem. Biophys. Acta 863:337-340.
Hein, L., Lullmann-Rauch, R., and Mohr, K. 1990. Human accumulation potential of xenobiotics: Potential of catamphiphilic drugs to promote their accumulation via inducing lipidosis or mucopolysaccharidosis. Xenobiotica 20:1259-1267.
Herbette, L., Katz, A. M., and Sturtevant, J. M. 1983. Comparisons of the interaction of propanolol and timolol with model and biological membrane systems. Mol. Pharmacol. 24:259-269.
Hoekstra, D., de Boer, T., Klappe, K., and Wilschut, J. 1984. Fluorescence method for measuring the kinetics of fusion between biological membranes. Biochemistry 23:5675-5681.
Hope, M. j., Bally, M. B., Webb, G., and Cullis, P. R. 1985. Production of large unilamellar vesicles by a rapid extrusion procedure. Characterization of size distribution, trapped volume and ability to maintain a membrane potential. Biochim. Biophys. Acta 812:55-65.
Hostetler, K. Y., and Hall, L. B. 1982. Inhibition of kidney lysosomal phospholipases A and C by aminoglycoside antibiotics: Possible mechanism of aminoglycoside toxicity. Proc. Natl Acad. Sci. USA 79:1663-1667.
Hostetler, K. Y., and Jellison, E. J. 1990. Inhibition of kidney phospholipase A1 by aminoglycosides is a novel variant of substrate depletion inhibition. J. Pharmacol. Exp. Ther. 254:188-191.
Hottendorf, G. H., and Gordon, L. 1980. Comparative low-dose nephrotoxicities of gentamicin, tobramycin and amikacin. Antimicrob. Agents Chemother. 18:176-181.
Houghton, D. C., Lee, D., Gilbert, D. N., and Bennett, W. M. 1986. Chronic gentamicin nephrotoxicity. Continued tubular injury with preserved glomerular filtration function. Am. J. Pathol. 123:183-194.
Hui, S. W., Boni, T., Stewart, T. P., and Isac, T. 1983. Identification of phosphatidylserine and phosphatidylcholine in calcium-induced phase separated domains. Biochemistry 22:3511-3516.
Ibrahim, S., Kishore, B. K., Lambricht, P., Laurent, G., and Tulkens, P. M. 1989. Effect of aminoglycosides and of coadministration of poly-l-aspartic acid on urinary phospholipids excretion in rats: A comparative study. 4th Int. Nephrotoxicity Symp. Guildford, U.K., Abstract 25.
In’t Veld, G., Driessen, A. J. M., and Konings, W. N. 1992. Effect of the unsaturation of phospholipid acyl chains on leucine transport of Lactococcus lactis and membrane permeability. Biochem. Biophys. Acta 1108:31-39.
Kahlmeter, G., and Dahlager, J. I. 1984. Aminoglycoside toxicity: A review of clinical studies published between 1975 and 1982. J. Antimicrob. Chemother. 13:9-22.
Kaloyanides, G. J. 1984a. Aminoglycoside-induced functional and biochemical defects in the renal cortex. Fundam. Appl. Toxicol. 4:930-943.
Kaloyanides, G. J. 1984b. Renal pharmacology of aminoglycoside antibiotics. Contrib. Nephrol. 42:148-167.
Kirschbaum, B. B. 1984. Interactions between renal brush border membranes and polyamines. J. Pharmacol. Exp. Ther. 229:409-416.
Kishore, B. K., Kallay, Z., Lambricht, P., Laurent, G., and Tulkens, P. M. 1990a. Mechanism of protection afforded by polyaspartic acid against gentamicin-induced phospholipidosis. I. Polyaspartic acid binds and displaces gentamicin from negatively-charged phospholipid layers. J. Pharmacol. Exp. Ther. 255:867-874.
Kishore, B. K., Lambricht, P., Laurent, G., Maldague, P., Wagner, R., and Tulkens, P. M. 1990b. Mechanism of protection afforded by polyaspartic acid against gentamicin-induced phospholipidosis. II. Comparative in vitro and in vivo studies with poly-L-aspartic, poly-L-glutamic and poly-D- glumatic acids. J. Pharmacol. Exp. Ther. 255:875-885.
Kishore, B. K., Ibrahim, S., Lambricht, P., Laurent, G., Maldague, P., and Tulkens, P. M. 1992. Comparative assessment of poly-L-aspartic and poly-L-glutamic acids against gentamicin-induced renal lysosomal phospholipidosis, phospholipiduria and cell proliferation in rats. J. Pharmacol. Exp. Ther. 262:424-432.
Kosek, J. C., Mazze, R. I., and Cousins, M. J, 1974. Nephrotoxicity of gentamicin. Lab. Invest. 30:48-57.
Kouaouci, R., Silvius, J. R., Graham, I., and Pdzolet, M. 1985. Calcium-induced lateral phase separations in phosphatidylcholine-phosphatidic acid mixtures. A Raman spectroscopic study. Biochemistry 24:7132-7140.
Kubo, M., Gardner, M. F., and Hostetler, K. Y. 1986. Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles. Contribution of ionic and hydrophobic forces. Biochem. Pharmacol. 35:3761-3765.
Kursch, B., Lullmann, H., and Mohr, K. 1983. Influence of various cationic amphiphilic drugs on the phase-transition temperature of phosphatidylcholine liposomes. Biochem. Pharmacol. 32:2589-2594.
Lakhdar-Ghazal, F., Vigroux, A., Willson, M., Tocanne, J. F., Pri, J., and Fayes, J. C. 1991. Interactions between trypanocidal drugs and membrane phospholipids. A surface pressure, surface potential and electrophoretic mobility study. Biochem. Pharmacol. 42:2099-2105.
Laroche, G., Carrier, D., and Pdzolet, M. 1988. Study of the effect of poly (L-lysine) on phosphatidic acid and phosphatidylcholine/phosphatidic acid bilayers by Raman spectroscopy. Biochemistry 27:6220-6228.
Laurent, G., and Tulkens, P. M. 1987. Aminoglycoside nephrotoxicity: Cellular and molecular aspects. ISI atlas of science!pharmacology 1:40-44.
Laurent, G., Carlier, M. B., Rollman, B., Van Hoof, F., and Tulkens, P. 1982. Mechanism of aminoglycoside-induced lysosomal phospholipidosis: In vitro and in vivo studies with gentamicin and amikacin. Biochem. Pharmacol. 31:3861-3870.
Laurent, G., Maldague, P., Carlier, M. B., and Tulkens, P. 1983. Increased renal DNA synthesis in vivo after administration of low doses of gentamicin to rats. Antimicrob. Agents Chemother. 24:586593.
Laurent, G., Maldague, P., Toubeau, G., Heuson-Stiennon, J. A., and Tulkens, P. M. 1988. Kidney tissue repair after nephrotoxic injury: Biochemical and morphological characterization. CRC Crit. Rev. Toxicol. 19:147-183.
Laurent, G., Kishore, B. K., and Tulkens, P. M. 1990. Aminoglycoside-induced phospholipidosis and nephrotoxicity (Commentary). Biochem. Pharmacol. 40:2383-2392.
Lee, A. G. 1976. Model for action of local anaesthetics. Nature (Lond.) 262:545-548.
Lietman, P. S. 1985. Aminoglycosides and spectinomycin: Aminocyclitols. In Principles and practice of infectious diseases, eds. G. L. Mandell, R. G. Douglas, and J. E. Bennet, pp. 192-206. New York: John Wiley & Sons.
Lipsky, J. J., and Lietman, P. S. 1982. Aminoglycoside inhibition of a renal phosphatidylinositol phospholipase C. J. Pharmacol. Exp. Ther. 220:287-292.
Lohdi, S., Weiner, N. D., and Schacht, J. 1976. Interactions of neomycin and calcium in synaptosomal membranes and polyphosphoinositide monolayers. Biochim. Biophys. Acta 426:781-785.
Lüllmann, H., and Vollmer, B. 1982. An interaction of aminoglycoside antibiotics with Ca binding to lipid monolayers and to biomembranes. Biochem. Pharmacol. 31:3769-3773.
Lüllmann, H., Lollmann-Rauch, R., and Wassermann, O. 1975. Drug-induced phospholipidosis. CRC Crit. Rev. Toxicol. 4:185-218.
Lüllmann-Rauch, R. 1979. Drug-induced lysosomal storage disorders. In Lysosomes in applied biology and therapeutics, vol. 6, eds. J. T. Dingle, P. J. Jacques, and H. I. Shaw, pp. 49-130. Amsterdam: North Holland.
Luxnat, M., and Galla, H. J. 1986. Partition of chlorpromazine into lipid bilayer membranes: The effect of membrane structure and composition. Biochim. Biophys. Acta 856:274-282.
Marichal, P., Vanden Bossche, H., Moereels, H., and Brasseur, R. 1990. Mode of insertion of azole anti- fungals and sterols in biological membranes. In Molecular description of biological membranes by computer aided conformational analysis. Part 2; Mode of insertion of amphiphilic components into the lipid membrane, ed. R. Brasseur, pp. 27-42. Boca Raton, Fla.: CRC Press.
Mazer, N. A., Carey, M. C., Kwasnick, R. F., and Benedek, G. B. 1979. Quasielastic light scattering studies of aqueous biliary lipid systems. Size, shape and thermodynamics of bile salt micelles. Biochemistry 18:3064-3075.
McGilvery, R. W. 1979. Biochemistry: A functional approach, p. 206. Philadelphia: W. B. Saunders.
McLaughlin, A. C., Cullis, P. R., Hemminga, M. A., Hoult, D. I., Radda, G. K., Ritchie, G. A., and Richards, R. E. 1977. Application of 3’P NMR to model and biological membrane systems. FEBS Lett. 57:213-218.
Mingeot-Leclercq, M. P., Laurent, G., and Tulkens, P. M. 1988. Biochemical mechanism of aminoglycoside-induced inhibition of phosphatidylcholine hydrolysis by lysosomal phospholipases. Biochem. Pharmacol. 37:591-599.
Mingeot-Leclercq, M. P., Schanck, A., Ronveaux-Dupal, M. F., Deleers, M., Brasseur, R., Ruysschaert, J. M., and Tulkens P. M. 1989. Ultrastructural, physico-chemical and conformational study of the interactions of gentamicin and bis(beta diethylaminoethylether) hexestrol with negatively charged phospholipid bilayers. Biochem. Pharmacol. 38:729-741.
Mingeot-Leclercq, M. P., Piret, J., Brasseur, R., and Tulkens, P. M. 1990a. Effect of acidic phospholipids on the activity of lysosomal phospholipases and on their inhibition by aminoglycoside antibiotics. I. Biochemical analysis. Biochem. Pharmacol. 40:489-497.
Mingeot-Leclercq, M. P., Piret, J., Tulkens, P. M., and Brasseur, R. 1990b. Effect of acidic phospholipids on the activity of lysosomal phospholipases and on their inhibition by aminoglycoside antibiotics. II. Conformational analysis. Biochem. Pharmacol. 40:499-506.
Mingeot-Leclercq, M. P., Laurent, G., Kishore, B. K., and Tulkens, P. M. 1991a. Aminoglycosides nephrotoxicity. Life Sci. Adv. (Biochem. Pharmacol.) 10:113-141.
Mingeot-Leclercq, M. P., Van Schepdael, A., Brasseur, R., Busson, R., Vanderhaeghe, H. J.-, Claes, P. J., and Tulkens, P. M. 1991b. New derivatives of Kanamycin B obtained by modifications and substitutions in position 6”. II. In vitro and computer-aided toxicological evaluation, with respect to interactions with phosphatidylinositol. J. Med. Chem. 34:1476-1482.
Moor, H., Muhlethaler, K., Waldner, H., and Frey-Wyssling, A. 1961. A new freezing-ultramicrotome. J. Biophys. Biochem. Cytol. 10:1-13.
Nagabhushan, T. L., Miller, C. H., and Weinstein, M. J. 1982. Structure-activity relationships in amino- glycoside-aminocyclitol antibiotics. In The aminoglycosides: Microbiology, clinical use and toxicology, eds. A. Whelton and H. C. Neu, pp. 3-27. New York: Marcel Dekker.
Nicolay, K., Sautereau, A. M., Tocanne, J. F., Brasseur, R., Huart, P., Ruysschaert, J. M., and de Kruijff, B. 1988. A comparative model membrane study on structural effects of membrane-active positively charged anti-tumor drugs. Biochim. Biophys. Acta 940:197-208.
Ohkuma, S., and Poole, B. 1978. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc. Natl. Acad. Sci. USA 75:3327-3331.
Ohyashiki, T., Ohtsuka, T., and Mohri, T. 1986. A change in the lipid fluidity of the porcine intestinal brush-border membranes by lipid peroxydation. Studies using pyrene and fluorescent stearic acid derivatives. Biochem. Biophys. Acta 861:311-318.
Papahadjopoulos, D., Jacobson, K., Nir, S., and Isac, T. 1973. Phase transitions in phospholipid vesicles. Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol. Biochim. Biophys. Acta 311:330-348.
Papahadjopoulos, D., Jacobson, K., Poste, G., and Shepherd, G. 1975. Effects of local anaesthetics on membrane properties. I. Changes in the fluidity of phospholipid bilayers. Biochim. Biophys. Acta 394:504-519.
Parker, R. A., Gilbert, D. N., Houghton, D. C., Porter, G. A., and Bennett, W. M. 1980. Comparative nephrotoxicities of high-dose netilmicin and tobramycin in rats. Antimicrob. Agents Chemother. 18:346-348.
Piret, J., Kishore, B. K., and Tulkens, P. M. 1992. Effect of substrate organization on the activity and on the mechanism of gentamicin-induced inhibition of rat liver lysosomal phospholipase A1. Biochem. Pharmacol. 43:895-898.
Ramaswami, V., Haaseth, R. C., Matsunaga, T. O., Hruby, V. J., and O’Brien, D. F. 1992. Opioid peptide interactions with lipid bilayer membranes. Biochim. Biophys. Acta 1109:195-202.
Ramsammy, L., and Kaloyanides, G. J. 1985. Gentamicin alters the physical properties of phosphatidylinositol liposomes. Fed. Proc. 44:1351A.
Ramsammy, L. S., and Kaloyanides, G. J. 1987. Effect of gentamicin on the transition temperature and permeability to glycerol of phosphatidylinositol-containing liposomes. Biochem. Pharmacol. 36:1179-1181.
Ramsammy, L. S., Josepovitz, C., Lane, B. P., and Kaloyanides, G. J. 1989. Polyaspartic acid protects against gentamicin nephrotoxicity in the rat. J. Pharmacol. Exp. Ther. 250:149-153.
Ramsammy, L., Josepovitz, C., Lane, B., and Kaloyanides, G. J. 1990. Polyaspartic acid inhibits gentamicin-induced perturbation of phospholipid metabolism. Am. J. Physiol. 258:0141-0149.
Reijngoud, D. J., and Tager, J. M. 1977. The permeability of the lysosomal membrane. Biochim. Biophys. Acta 472:419-449.
Sande, M. A., and Mandell, G. L. 1990. Antimicrobial agents: the aminoglycosides. In The pharmacological basis of therapeutics, 8th ed., eds. A. Goodman-Gilman, T. W. Rail, A. S. Nies, and P. Taylor, pp. 1098-1116. New York: Pergamon.
Schanck, A., Brasseur, R., Mingeot-Leclercq, M. P., and Tulkens, P. M. 1992a. Interactions of aminoglycosides with phosphatidylinositol: A,5N nuclear magnetic resonance study. Magn. Reson. Chem. 30:11-15.
Schanck, A., Mingeot-Leclercq, M. P., Tulkens, P. M., Carrier, D., Smith, I. C. P., and Jarrel, H. C. 1992b. Interactions of aminoglycosides with phospholipids. A deuterium nuclear magnetic resonance study. Chem. Phys. Lipids 62:153-163.
Schwertz, D. W., Kreisberg, J. I., and Venkatachalam, M. A. 1984. Effects of aminoglycosides on proximal tubule brush border membrane phosphatidylinositol-specific phospholipase C. J. Pharmacol. Exp. Ther. 231:48-55.
Shinitzky, M., and Barenholz, Y. 1974. Dynamics of the hydrocarbon layer in liposomes of lecithin and sphingomyelin containing dicethylphosphate. J. Biol. Chem. 249:2652-2657.
Silvius, J. R. 1990. Calcium-induced lipid phase separations and interactions of phosphatidylcholine/- anionic phospholipid vesicles. Fluorescence studies using carbazole-labeled and brominated phospholipids. Biochemistry 29:2930-2938.
Smith, R., and Cornell, B. A. 1985. Myelin basic protein induces hexagonal phase formation in dispersion of diacylphosphatidic acid. Biochem. Biophys. Acta 818:275-279.
Struck, D. K., Hoekstra, D., and Pagano, R. E. 1981. Use of resonance energy transfer to monitor membrane fusion. Biochemistry 20:4093-4099.
Taraschi, T. F., de Kruijff, B., Verkleij, A., and Van Echteld, C. J. 1982. Effect of glycophorin on lipid polymorphism. A 3,P-NMR study. Biochem. Biophys. Acta 685:153-161.
Thomas, P. G., and Verkleij, A. J. 1990. The dissimilar interactions of the calcium antagonist flunarizine with different phospholipidd classes and molecular species: A differential scanning calorimetry study. Biochim. Biophys. Acta 1030:211-222.
Toubeau, G., Laurent, G., Carlier, M. B., Abid, S., Maldague, P., Heuson-Stiennon, J., and Tulkens, P. M. 1986. Tissue repair in rat kidney cortex during short treatment with aminoglycosides at low doses: A comparative biochemical and morphometric study. Lab. Invest. 54:385-393.
Tournois, H., Fabrie, C. H. J., Burger, K. N. J., Mandersloot, J., Hilgers, P., van Dalen, H., and de Kruijff, B. 1990. Gramicidin A induced fusion of large unilamellar dioleoylphosphatidylcholine vesicles and its relation to the induction of type II nonbilayer structures. Biochemistry 29:8297-8307.
Tulkens, P. M. 1986. Experimental studies on nephrotoxicity of aminoglycosides at low doses: Mechanisms and perspectives. Am. J. Med. 80(6B):105-114.
Tulkens, P. M. 1989. Nephrotoxicity of aminoglycosides. Toxicol. Lett. 46:107-123.
Tulkens, P. M. 1991a. Efficacy and safety of aminoglycosides once-a-day: Experimental and clinical data. Scand. J. Infect. Dis. Suppl. 74:249-257.
Tulkens, P. M. 1991b. Pharmacokinetic and toxicological evaluation of the once-a-day regimen versus conventional schedules of netilmicin and amikacin. /. Antimicrob. Chemother. 27(C):49-61.
Tulkens, P. M., De Broe, M. E., Maldague, P., and Heuson-Stiennon, J. 1984. The role of lysosomes in aminoglycoside-induced nephrotoxicity. In Acute renal failure: Correlations between morphology and function, eds. K. Solez and A. Whelton, pp. 299-327. New York: Marcel Dekker.
Tulkens, P. M., Mingeot-Leclercq, M. P., Laurent, G., and Brasseur, R. 1990. Conformational and biochemical analysis of the interactions phospholipids-aminoglycoside antibiotics in relation with their toxicity. In Molecular description of biological membrane components by computer-aided conformational analysis, vol. II, ed. R. Brasseur, pp. 63-93. Boca Raton, Fla.: CRC Press.
Vaamonde, C. A., Laurent, G., Beauchamp, D., Carlier, M. B. Ibrahim, S., Maldague, P., and Tulkens, P. M. 1986. Renal phospholipidosis and cellular response of diabetic and control rats to low, nontoxic doses of gentamicin. Kidney Int. 29:311.
Van Bambeke, F., Mingeot-Leclercq, M. P., Schanck, A., Brasseur, R., and Tulkens, P. M. 1993. Alterations in membrane permeability induced by aminoglycoside antibiotics: Studies on liposomes and cultured cells. Eur. J. Pharmacol. 247:155-168.
Van Bambeke, F., Mingeot-Leclerq, M.-P., Brasseur, R., Tulkens, P. M., and Schanck, A. Aminoglycoside antibiotics prevent the formation of inverted micelles in negatively-charged membranes. Comparative studies using melittin and spermine (submitted).
Van Bambeke, F., Tulkens, P. M., Brasseur, R., and Mingeot-Leclercq, M.-P. Aminoglycoside antibiotics induce aggregation but not fusion of negatively-charged liposomes. Comparative studies using melittin and spermine (submitted).
Van Dijck, P. W. M., Ververgaert, P. H.J., Verkleij, A. J., Van Deenen, L. L. M. and De Gier, J. 1975. Influence of Ca2+ and Mg2+ on the thermotropic behaviour and permeability properties of liposomes prepared from dimyristoyl phosphatidylglycerol and mixtures of DMPG and DMPC. Biochim. Biophys. Acta 406:465-478.
Van Echteld, C. J., De Kruijff, B., Verkleij, A. f., Leunissen-Bijvelt, j., and De Gier, J. 1982. Gramicidin induces the formation of non-bilayer structures in phosphatidylcholine dispersions in a fatty acid chain length dependent way. Biochim. Biophys. Acta 692:126-138.
van Hoogevest, P., de Gier, and de Kruijff, B. 1984. Determination of the size of the packing defects in dimyristoylphosphatidylcholine bilayers, present at the phase transition temperature. FEBS Lett. 171(21):160-164.
Van Schepdael, A., Busson, R., Verbist, L., Vanderhaeghe, H. J., Mingeot-Leclercq, P. M., Brasseur, R., and Tulkens, P. M. 1991a. Synthesis, antibacterial activity and toxicological evaluation (in vitro and computer-aided) of 1-C-hydroxylmethyl kanamycin B and 1-C-hydroxymethyl, 6”-chlorokanamycin B. J. Med. Chem. 34:1483-1492.
Van Schepdael, A., Delcourt, J., Mulier, M., Busson, R., Mingeot-Leclercq, M. P., Tulkens, P. M., and Claes, P. J. 1991b. New derivatives of kanamycin B obtained by modifications and substitutions in position 6”. I. Synthesis and microbiological evaluation. J. Med. Chem. 34:1468-1475.
Vasilenko, I., De Kruijff, B., and Verkleij, A. J. 1982. Polymorphic phase behaviour of cardiolipin from bovine heart and from Bacillus subtilis as detected by31P-NMR and freeze-fracture techniques. Effects of Ca2+, Mg2+, Ba2+ and temperature. Biochim. Biophys. Acta 684:282-286.
Verkleij, A. j. 1984. Lipidic intramembranous particles. Biochim. Biophys. Acta 779:43-63.
Verkleij, A. J., De Maagd, R., and Leunissen-Bijvelt, J. 1982. Divalent cations and chlorpromazine can induce non-bilayer structures in PA containing model membranes. Biochim. Biophys. Acta 684:255262.
Wang, B. M., Weiner, N. D., Takada, A., and Schacht, J. 1984. Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing. Biochem. Pharmacol. 33:3257-3262.
Weinstein, J. N., Yoshikami, S., Henkart, P., Blumenthal, R., and Hagins, W. A. 1977. Liposome-cell interaction: transfer and intracellular release of a trapped fluorescent marker. Science 195:489-491.
Wiener, J. R., Pal, R., Barenholz, Y., and Wagner, R. 1985. Effect of the vesicular stomatitis virus matrix protein on the lateral organization of lipid bilayers containing phosphatidylglycerol: Use of fluorescent phospholipid analogues. Biochemistry 24:7651-7658.
Williams, P. D., and Hottendorf, G. H. 1985. Inhibition of renal membrane binding and nephrotoxicity of gentamicin by polyasparagine and polyaspartic acid in the rat. Res. Commun. Chem. Pathol. Pharmacol. 47:317-320.
Williams, P. D., Hottendorf, G. H., and Bennett, D. B. 1986. Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237:919-925.
Yeagle, P. L. 1989. Lipid regulation of cell membrane structure and function. FASES J. 3:1833-1842.
