Negre-Salvayre A, Alomar Y, Troly M, Salvayre R
Laboratoire de Biochimie, C.H.U. Rangueil, Toulouse, France.
Biochim Biophys Acta. 1991 Jun 5;1096(4):291-300. doi: 10.1016/0925-4439(91)90065-h.
Comparison of the protective effect of three antioxidants (from three different chemical classes) against cell injury due to LDL oxidation, allowed us to clearly discriminate between two different lines of defence. The ultraviolet-induced lipid peroxidation of LDL was strongly inhibited by 10 mumol/l catechin and 25 mumol/l probucol, but only poorly by 100 mumol/l vitamin E. The ultraviolet-treated LDL protected by catechin or probucol (i.e. LDL irradiated by ultraviolet in the presence of effective concentrations of antioxidants inhibiting the lipid peroxidation) were much less 'cytotoxic' than unprotected ultraviolet-treated LDL. In contrast, LDL treated by ultraviolet in the presence of 100 mumol/l vitamin E were 'cytotoxic' similarly to unprotected LDL. The level of 'cytotoxicity' of LDL treated by ultraviolet in the presence of antioxidants (protected ultraviolet-treated LDL) was well correlated with their content in lipid peroxidation markers. Therefore these markers can be useful for predicting the 'cytotoxicity' of oxidized LDL and subsequently the protective effect of the tested antioxidants. The 'cytotoxicity' of unprotected ultraviolet-treated LDL (i.e. LDL irradiated by ultraviolet in the absence of exogenous antioxidant) can be effectively blocked by preincubation of the cells with antioxidants. Catechin (10 mumol/l) and vitamin E (100 mumol/l) are very effective cytoprotective agents, whereas probucol (up to 50 mumol/l) was completely ineffective under these experimental conditions. The cytoprotective effect of vitamin E was associated to a complete inhibition of the cellular TBARS formation induced by ultraviolet-treated LDL, whereas the cytoprotective effect of catechin was relatively independent on the TBARS inhibition. All these results showed that: (1) probucol (25 mumol/l) is very effective to prevent lipid peroxidation of LDL and their subsequent 'cytotoxicity', but it cannot protect cells against the 'cytotoxicity' of previously oxidized LDL; (2) vitamin E (100 mumol/l) prevents poorly the ultraviolet-induced lipid peroxidation of LDL, but is able to block simultaneously the cellular oxidative stress and the 'cytotoxicity' induced by previously oxidized LDL; and (3) catechin (10 mumol/l) exhibited two types of protective effects: it inhibits the lipid peroxidation of LDL (and their subsequent 'cytotoxicity') and very effectively protects the cells against 'toxicity' of previously oxidized LDL (with only little inhibition of the cellular oxidative stress).(ABSTRACT TRUNCATED AT 400 WORDS)
比较三种抗氧化剂（来自三种不同化学类别）对低密度脂蛋白（LDL）氧化所致细胞损伤的保护作用，使我们能够清楚地区分两种不同的防御机制。10 μmol/L儿茶素和25 μmol/L普罗布考能强烈抑制紫外线诱导的LDL脂质过氧化，但100 μmol/L维生素E的抑制作用较弱。经儿茶素或普罗布考保护的紫外线处理的LDL（即在有效浓度的抗氧化剂存在下经紫外线照射的LDL，这些抗氧化剂抑制脂质过氧化）的“细胞毒性”远低于未受保护的紫外线处理的LDL。相反，在100 μmol/L维生素E存在下经紫外线处理的LDL与未受保护的LDL具有相似的“细胞毒性”。在抗氧化剂存在下经紫外线处理的LDL（受保护的紫外线处理的LDL）的“细胞毒性”水平与其脂质过氧化标志物的含量密切相关。因此，这些标志物可用于预测氧化LDL的“细胞毒性”以及随后所测试抗氧化剂的保护作用。未受保护的紫外线处理的LDL（即在没有外源性抗氧化剂的情况下经紫外线照射的LDL）的“细胞毒性”可通过细胞与抗氧化剂预孵育而有效阻断。儿茶素（10 μmol/L）和维生素E（100 μmol/L）是非常有效的细胞保护剂，而在这些实验条件下，普罗布考（高达50 μmol/L）完全无效。维生素E的细胞保护作用与完全抑制紫外线处理的LDL诱导的细胞丙二醛（TBARS）形成有关，而儿茶素的细胞保护作用相对独立于TBARS抑制。所有这些结果表明：（1）普罗布考（25 μmol/L）能非常有效地防止LDL的脂质过氧化及其随后的“细胞毒性”，但它不能保护细胞免受先前氧化的LDL的“细胞毒性”；（2）维生素E（100 μmol/L）对紫外线诱导的LDL脂质过氧化的预防作用较差，但能够同时阻断细胞氧化应激和先前氧化的LDL诱导的“细胞毒性”；（3）儿茶素（10 μmol/L）表现出两种保护作用：它抑制LDL的脂质过氧化（及其随后的“细胞毒性”），并非常有效地保护细胞免受先前氧化的LDL的“毒性”（对细胞氧化应激的抑制作用很小）。（摘要截短至400字）
