Ogiso T, Ito Y, Iwaki M, Nakanishi K, Saito H
Chem Pharm Bull (Tokyo). 1989 Feb;37(2):430-4. doi: 10.1248/cpb.37.430.
The phospholipid organization, lipid fluidity and spectrin degradation were measured in human erythrocytes oxidized with phenylhydrazine, and the contribution of these structural alterations to the penetration of perazine and promethazine into the membrane was estimated. It was found that exposure of erythrocytes to phenylhydrazine (0.2--0.4 mg/ml) produced a 35--40% decrease in the amount of spectrin, with resultant gross morphological changes to the echinocyte conformation. The phosphatidylethanolamine content in the treated erythrocytes was greatly lowered compared with that in the untreated cells. Treatment with phenylhydrazine (0.05--0.2 mg/ml) dramatically diminished the lipid fluidity of the membrane, as estimated by electron spin resonance (ESR) spectrometry, and the ESR study revealed increased restriction of the molecular motion of the hydrophobic core in the treated membrane. These results suggest a drastic alteration of the erythrocyte membrane structure. The amount of drugs which penetrated into the treated erythrocytes increased markedly with increasing phenylhydrazine concentration, suggesting enhanced membrane permeability and facilitated localization of the drugs in the hydrophobic regions due to the structural changes and partial disturbance of the lipid organization.
对用苯肼氧化的人红细胞进行磷脂组织、脂质流动性和血影蛋白降解的测定，并评估这些结构改变对奋乃静和异丙嗪渗透进入细胞膜的作用。结果发现，将红细胞暴露于苯肼（0.2 - 0.4毫克/毫升）会使血影蛋白量减少35 - 40%，导致红细胞呈现棘状红细胞构象的总体形态变化。与未处理细胞相比，经处理的红细胞中磷脂酰乙醇胺含量大幅降低。通过电子自旋共振（ESR）光谱法估计，用苯肼（0.05 - 0.2毫克/毫升）处理可显著降低膜的脂质流动性，并且ESR研究显示，处理后的膜中疏水核心分子运动的受限程度增加。这些结果表明红细胞膜结构发生了剧烈改变。随着苯肼浓度增加，渗透进入经处理红细胞的药物量显著增加，这表明由于结构变化和脂质组织的部分紊乱，膜通透性增强且药物在疏水区域的定位变得更容易。
