Effect of beta-lactam antibiotics on lipid bilayer membranes. II. Cephalosporin antibiotics

Interaction of cephalosporin antibiotics with flat bilayer lipid membranes (BLM) composed of vegetative or bacterial phospholipids was studied with respect to their effect on electroconductivity, capacity for binding to the bilayers and capacity for transmembrane transfer through the bilayers. By their effect on conductivity, the investigated cephalosporins could be divided into three groups: those having no effect on conductivity at the maximum concentrations (up to 1 mg/ml) i.e. cefoperazone, cefotaxime and ceftizoxime, those having an effect on conductivity at concentrations of 0.2 to 0.5 mg/ml i.e. cephalexin and cephalothin and those having a significant effect on conductivity at concentrations of 10 to 60 micrograms/ml i.e. N-acyl derivative of 7-ACA (substance 64) and 7-ACA derivative (substance 71). The cephalosporins had a capacity for binding to the bilayers and for incorporation into the bilayers. They penetrated to some extent through the bilayers composed of either vegetable or bacterial phospholipids. The lower rate of penetration through the BLM as compared to that of penicillins must be due to lower hydrophobicity of the cephalosporin molecules as compared to that of penicillins.     

Effect of beta-lactam antibiotics on lipid bilayer membranes. I. Penicillin antibiotics

Interaction between penicillins and model membrane systems, flat black bilayer lipid membranes (BLM) composed of vegetable or bacterial phospholipids was studied with an account of the complicated structure of bacterial cell membranes and possible presence in them of "pure" bilayer lipid areas. By their effect on electroconductivity of the BLM the antibiotics could be divided into three groups: those having no effect on the BLM electroconductivity at the maximum concentrations i.e. benzylpenicillin, carbenicillin, piperacillin (at pH 6.0 and 7.0) and ampicillin (at pH 6.0), those insignificantly changing electroconductivity of the BLM i.e. carfecillin and azlocillin and those having a significant effect on the BLM electroconductivity i.e. ampicillin N-acyl derivatives and 6-APA. The effect of ampicillin on the BLM conductivity markedly depended on the electrolite pH. The penicillins bound to the bilayer and induced changes in the transmembrane potential (evident from the changes in the second harmonic of the capacitive current) and the BLM elasticity-capacitance parameters (evident from the changes in the ratio of the amplitudes of the first and third harmonics). It was shown that all the penicillins penetrated through the BLM composed of either vegetable or bacterial phospholipids. The capacity for the transmembrane transfer without changing of the bilayer conductivity must be connected with the fact that the penetrating antibiotics did not induce any changes in the BLM structure. The effect on the conductivity probably depended in its turn on the form of the molecule and the ratio of the hydrophilic and hydrophobic parts in it.     

Role of antibiotics in lipid peroxidation.

Alterations in the levels of lipid peroxides, superoxide dismutase, catalase, glutathione, free fatty acid and serum ceruloplasmin were studied in rats fed with high fat cholesterol diet administered different antibiotics, viz. ampicillin, tetracycline, streptomycin, chloramphenicol and cephalosporin. The concentrations of lipid peroxides, glutathione, free fatty acid decreased in most of the tissues, except in tetracycline, streptomycin and cephalosporin treated rats. The changes observed in the activities of superoxide dismutase and catalase in the liver and kidney of these antibiotics administered groups also are in accordance with the changes in lipid peroxides. The results show that the tetracycline is hepatotoxic and nephrotoxic, while cephalosporin and streptomycin are nephrotoxic.