Nemeikaite-Ceniene Ausra, Sergediene Egle, Nivinskas Henrikas, Cenas Narimantas
Institute of Immunology, Vilnius, Lithuania.
Z Naturforsch C J Biosci. 2002 Sep-Oct;57(9-10):822-7. doi: 10.1515/znc-2002-9-1012.
In order to assess the role of oxidative stress in the cytotoxicity of natural hydroxyanthraquinones, we compared rhein, emodin, danthron, chrysophanol, and carminic acid, and a series of model quinones with available values of single-electron reduction midpoint potential at pH 7.0 (E(1)7), with respect to their reactivity in the single-electron enzymatic reduction, and their mammalian cell toxicity. The toxicity of model quinones to the bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK), and HL-60, a human promyelocytic leukemia cell line, increased with an increase in their E(1)7. A close parallelism was found between the reactivity of hydroxyanthraquinones and model quinones with single-electron transferring flavoenzymes ferredoxin: NADP+ reductase and NADPH:cytochrome P450 reductase, and their cytotoxicity. This points to the importance of oxidative stress in the toxicity of hydroxyanthraquinones in these cell lines, which was further evidenced by the protective effects of desferrioxamine and the antioxidant N,N'-diphenyl-p-phenylene diamine, by the potentiating effects of 1,3-bis-(2-chloroethyl)-1-nitrosourea, and an increase in lipid peroxidation.
为了评估氧化应激在天然羟基蒽醌细胞毒性中的作用，我们比较了大黄酸、大黄素、丹蒽醌、 Chrysophanol和胭脂红酸，以及一系列在pH 7.0时具有单电子还原中点电位（E(1)7）可用值的模型醌，比较了它们在单电子酶促还原中的反应性及其对哺乳动物细胞的毒性。模型醌对牛白血病病毒转化的羔羊肾成纤维细胞（FLK系）和人早幼粒细胞白血病细胞系HL-60的毒性随其E(1)7的增加而增加。羟基蒽醌和模型醌与单电子转移黄素酶铁氧还蛋白：NADP +还原酶和NADPH：细胞色素P450还原酶的反应性与其细胞毒性之间存在密切的平行关系。这表明氧化应激在这些细胞系中羟基蒽醌毒性中的重要性，去铁胺和抗氧化剂N，N'-二苯基对苯二胺的保护作用、1,3-双（2-氯乙基）-1-亚硝基脲的增强作用以及脂质过氧化的增加进一步证明了这一点。
