Lipid peroxidation and loss of potassium from red blood cells produced by phototoxic quinolones.
Alterations of the cationic permeability of red blood cell membranes induced by the photosensitiser nalidixic acid were demonstrated by evaluating the potassium loss from intact erythrocytes. The results show that an increase in intracellular potassium efflux, precedes the photohemolysis induced by nalidixic acid. The addition of a nonpermeable osmotic solute, such as sucrose, inhibited photohemolysis but not the potassium loss, indicating a colloid osmotic lysis. Lipid peroxidation induced by nalidixic acid and other photosensitiser quinolones (oxolinic acid and rosoxacin) was time irradiation-dependent. Although rosoxacin was the most photoperoxidative, none of the three quinolones studied produced significant lipid peroxidation. However, of the three quinolones studied, only rosoxacin considerably diminished the percentage of the cholesterol extracted from red blood cell membranes. It is postulated that the increased cation permeability induced by nalidixic and oxolinic acids cannot be attributed to cholesterol oxidation nor to lipid peroxidation; a more probable mechanism is photo-oxidation of amino acid residues of the membrane proteins. However, the lysis induced by rosoxacin is caused by photo-oxidation of cholesterol, not excluding other cellular targets.
Cárdenas
A M
AM
Laboratorio de Fotobiologia y Fotoquimica, Facultad de Medicina, Universidad de Valparaiso, Chile.
Cortés
M P
MP
Fernández
E
E
Peña
W
W
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D009268:Nalidixic Acid / Q000633:toxicity*; D010084:Oxidation-Reduction; D010093:Oxolinic Acid / Q000633:toxicity*; D010782:Photolysis / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D015363:Quinolones / Q000633:toxicity*
D042462:4-Quinolones; D000890:Anti-Infective Agents; D015363:Quinolones; D009268:Nalidixic Acid; C021083:rosoxacin; D002784:Cholesterol; D010093:Oxolinic Acid; D011188:Potassium