Cárdenas A M, Cortés M P, Fernández E, Peña W
Laboratorio de Fotobiologia y Fotoquimica, Facultad de Medicina, Universidad de Valparaiso, Chile.
Toxicology. 1992;72(2):145-51. doi: 10.1016/0300-483x(92)90108-q.
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.
通过评估完整红细胞的钾流失情况,证实了光敏剂萘啶酸诱导的红细胞膜阳离子通透性变化。结果表明,细胞内钾外流增加先于萘啶酸诱导的光溶血。添加不可渗透的渗透溶质(如蔗糖)可抑制光溶血,但不能抑制钾流失,表明这是一种胶体渗透裂解。萘啶酸和其他光敏喹诺酮类药物(恶喹酸和咯索沙星)诱导的脂质过氧化具有时间辐射依赖性。尽管咯索沙星的光氧化作用最强,但所研究的三种喹诺酮类药物均未产生显著的脂质过氧化。然而,在所研究的三种喹诺酮类药物中,只有咯索沙星能显著降低从红细胞膜中提取的胆固醇百分比。据推测,萘啶酸和恶喹酸诱导的阳离子通透性增加不能归因于胆固醇氧化或脂质过氧化;更可能的机制是膜蛋白氨基酸残基的光氧化。然而,咯索沙星诱导的裂解是由胆固醇的光氧化引起的,不排除其他细胞靶点。