ABSTRACT
The interaction of gentamicin with monomolecular films of a series of biologically important lipids spread on an aqueous buffered subphase was studied. The surface pressure, pi, of these films was determined by the Wilhelmy plate method as a function of surface area, A, and pi-A curves were constructed. Changes in the pi-A characteristics in the presence of gentamicin were used as a measure of antibiotic-film interaction. No interaction was observed between gentamicin and films of cholesterol, egg lecithin, dipalmitoyl lecithin, phosphatidyl ethanolamine, stearyl alcohol, and bovine ceramides at all pH values studied. Stearic acid films showed no interaction with gentamicin at pH 5. At pH 7 and 8, a small increase in pressure (approximately 3 dynes/cm) was noted. A dramatic increase in surface pressure was observed in the presence of stearyl aldehyde films ranging from approximately 9 dynes/cm at pH 7,2 to 23 dynes/cm at pH 8.4. This effect was attributed to a Schiff-base reaction between the nonprotonated primary amino groups on the gentamicin molecule and the stearyl aldehyde. Further evidence was reported by the fact that the addition of glucose (which has been reported to participate in Schiff-base formation with amines) to the subphase inhibited the stearyl aldehyde-gentamicin interaction. Sucrose did not show a corresponding effect. The addition of sodium bisulfite, which reacts with aldehydes to form alpha-hydroxysulfonic acid, also inhibited the gentamicin-stearyl aldehyde interaction. It is postulated that Schiff-base formation is a step in the in vivo transport of gentamicin across the membrane of sensitive organisms.
Subject(s)
Gentamicins , Lipids , Chemical Phenomena , Chemistry , Cholesterol , Hydrogen-Ion Concentration , Membranes, Artificial , Phosphatidylcholines , Phosphatidylethanolamines , Phospholipids , Surface Properties , TemperatureSubject(s)
Heart/drug effects , Malate Dehydrogenase/antagonists & inhibitors , Myocardium/enzymology , Phosphatidylcholines/pharmacology , Phosphatidylethanolamines/pharmacology , Animals , Buffers , Cattle , Drug Stability , Eggs , NAD/metabolism , Oxaloacetates/pharmacology , Phosphates , Spectrophotometry, Ultraviolet , Swine , Time FactorsSubject(s)
Polysaccharides , Suspensions , Bismuth , Carbonates , Flocculation , Nitrates , Oxides , Parabens , Sulfaguanidine , Talc , Viscosity , Water , Xanthomonas , ZincSubject(s)
Membranes, Artificial , Animals , Benzoates , Humans , Malate Dehydrogenase , Methods , Myocardium/enzymology , Palmitic Acids , Phosphatidylcholines , Pressure , Serum Albumin , Sodium Chloride , Solvents , Surface Properties , Swine , Technology, Pharmaceutical , WaterSubject(s)
Cholesterol , Phosphatidylcholines , Cholesterol/analysis , Ketones/analysis , Oxidation-Reduction , Temperature , Time FactorsSubject(s)
Gentamicins/metabolism , Aldehydes , Biological Transport, Active , Cell Membrane/metabolism , Chemical Phenomena , Chemistry , Escherichia coli/drug effects , Gentamicins/pharmacology , Hydrogen-Ion Concentration , Membranes/metabolism , Schiff Bases , Sulfites/pharmacology , Surface Properties , Time FactorsABSTRACT
The autoxidative formation of 7-ketocholesterol and diols from aqueous cholesterol dispersions and from cholesterol monomolecular films has been studied as a function of time. The rate of oxidation of cholesterol is much faster at the surface than in the bulk. Whereas more than one-half of the cholesterol is oxidized at the surface within 8 hr at room temperature, no noticeable reaction was observed for the oxidation of cholesterol from aqueous dispersions at room temperature during this time period. However, similar rates of oxidation were observed when the dispersions were maintained at 85 degrees C.
Subject(s)
Cholesterol , Chemical Phenomena , Chemistry , Colloids , Ketosteroids/chemical synthesis , Kinetics , Macromolecular Substances , Membranes, Artificial , Oxidation-Reduction , Spectrophotometry , Stearic Acids , Sterols/chemical synthesis , Temperature , Ultraviolet RaysSubject(s)
Structure-Activity Relationship , Surface-Active Agents/pharmacology , Acetylcholine/pharmacology , Anesthetics, Local/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Biological Transport, Active , Carcinogens/pharmacology , Cell Membrane Permeability , Gases/pharmacology , Histamine H1 Antagonists/pharmacology , Hormones/pharmacology , Hypnotics and Sedatives/pharmacology , Isotonic Solutions , Membranes, Artificial , Phenothiazines/pharmacology , Pressure , Surface Properties , Surface Tension , Vitamins/pharmacologySubject(s)
Cholesterol , Membranes, Artificial , Nitrates , Nitrogen Dioxide , Air , Air Pollution , Cholestanes , Cholestanol , Chromatography, Thin Layer , Drug Stability , Esters , Molecular Biology , Oxidation-Reduction , Sterols , Surface Properties , Time FactorsABSTRACT
The pi-A characteristics of seven known oxidation products of cholesterol were determined. In all cases, the oxidation products yielded films which were more expanded than the film of cholesterol. Shifts in the position of the functional polar groups or the double bond within the sterol molecule results in marked changes in the pi-A curves. Furthermore, replacement of the 3-hydroxy group by a keto group results in a significant decrease in the collapse pressure of the films. Mixed films of each of the oxidation products with dipalmitoyl glycerylphosphorylcholine, egg lecithin, and cholesterol showed marked condensation effects. However, the data suggest that if air oxidation of cholesterol did occur at a biological membrane containing cholesterol and phospholipids, the permeability characteristics and other properties of the membrane might not be altered significantly.
