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γ射线对不同组成的脂质体的损伤及其受氮氧化物的保护作用

Gamma-irradiation damage to liposomes differing in composition and their protection by nitroxides.

作者信息

Samuni A M, Barenholz Y, Crommelin D J, Zuidam N J

机构信息

Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

出版信息

Free Radic Biol Med. 1997;23(7):972-9. doi: 10.1016/s0891-5849(97)00123-8.

Abstract

The present study aims to determine the effect of bilayer composition on oxidative damage and the protection against it in lipid multicomponent membranes. Irradiation damage in 200-nm liposomes and the protection provided by the nitroxide radicals, 2,2,6,6-tetramethylpiperidine-1-oxyl (Tempo) and 4-hydroxy-2,2,6,6-tetramethylpiperidine--1-oxyl (Tempol) were assessed by monitoring several chemical and physical parameters. Liposomes were prepared in four different lipid compositions (mole ratios), DPPC:DPPG 10:1; DPPC:DPPG:cholesterol 10:1:4; EPC:EPG 10:1; and EPC:EPG:cholesterol 10:1:4, and gamma-irradiated with a dose of 32 kGy. Lipid degradation was determined by HPLC and GC analyses, whereas size and differential scanning calorimetry measurements were used to monitor physical changes in the liposomal dispersions. The results indicate that: (1) addition of 5 mM Tempo or Tempol, or freezing of the sample inhibited radiation-induced lipid degradation; (2) Tempo and Tempol caused neither physical nor chemical changes in the liposomal dispersions; and (3) both nitroxides prevented or reduced some of the radiation-induced changes in thermotropic characteristics of the liposomes, preventing a shift in the temperature of the maximum of the main phase transition.

摘要

本研究旨在确定双层组成对脂质多组分膜氧化损伤及其防护作用的影响。通过监测多个化学和物理参数,评估了200纳米脂质体中的辐射损伤以及氮氧自由基2,2,6,6-四甲基哌啶-1-氧基(Tempo)和4-羟基-2,2,6,6-四甲基哌啶-1-氧基(Tempol)提供的防护作用。脂质体采用四种不同的脂质组成(摩尔比)制备:二棕榈酰磷脂酰胆碱(DPPC):二棕榈酰磷脂酰甘油(DPPG)10:1;DPPC:DPPG:胆固醇10:1:4;蛋黄卵磷脂(EPC):蛋黄磷脂酰甘油(EPG)10:1;以及EPC:EPG:胆固醇10:1:4,并以32千戈瑞的剂量进行γ射线辐照。通过高效液相色谱(HPLC)和气相色谱(GC)分析确定脂质降解,而通过尺寸和差示扫描量热法测量来监测脂质体分散体的物理变化。结果表明:(1)添加5毫摩尔Tempo或Tempol,或样品冷冻可抑制辐射诱导的脂质降解;(2)Tempo和Tempol在脂质体分散体中既未引起物理变化也未引起化学变化;(3)两种氮氧自由基均可预防或减少脂质体热致特性的一些辐射诱导变化,防止主相变最大值温度的偏移。

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