Braguini Welligton L, Gomes Maria A Biazon, de Oliveira Brás H, Carnieri Eva G S, Rocha Maria Eliane M, de Oliveira Maria Benigna M
Departamento de Bioqui;mica, Universidade Federal do Paraná, C.P. 19046, Curitiba, Paraná, 81531-990, Brazil.
Toxicol Lett. 2003 Jun 5;143(1):83-92. doi: 10.1016/s0378-4274(03)00074-2.
Isosteviol lactone (LAC), a lactone derivative of the diterpenic acid isosteviol (ISO) was evaluated for its effect on the oxidative metabolism of mitochondria isolated from rat liver. In this model, LAC (1 mM) depressed the phosphorylation efficiency, as shown by the decreased respiratory control coefficient (RCC) and ADP/O ratio. LAC (1 mM) inhibited NADH oxidase (45%), succinate oxidase (34%) and promoted low-level inhibitions on succinate dehydrogenase (13%), succinate-cytochrome c oxide-reductase (23%), cytochrome c oxidase (10%), and NADH dehydrogenase (13%). Glutamate dehydrogenase was also a target for LAC, as it was 85% inhibited by 1 mM LAC. Cyclic voltammetry data showed that LAC, as well as ISO, does not undergo redox reactions under current experimental conditions. LAC (0.05-0.75 mM) inhibited the swelling dependent on the glutamate oxidation, 50% of the effect occurring at 0.5 mM LAC. Swelling supported by KNO(3) and valinomycin was also inhibited over all concentrations used of LAC and ISO, the effect being of a lower intensity for LAC, suggesting that the modification of the structure of ISO by lactonization diminished its interaction with the membrane. This could contribute to attenuation of the toxic effects described for ISO on mitochondrial function, such as those on respiratory chain enzymatic complexes and phosphorylating activity.
异甜菊醇内酯（LAC）是二萜酸异甜菊醇（ISO）的内酯衍生物，本研究评估了其对从大鼠肝脏分离的线粒体氧化代谢的影响。在该模型中，LAC（1 mM）降低了磷酸化效率，表现为呼吸控制系数（RCC）和ADP/O比值降低。LAC（1 mM）抑制了NADH氧化酶（45%）、琥珀酸氧化酶（34%），并对琥珀酸脱氢酶（13%）、琥珀酸-细胞色素c氧化还原酶（23%）、细胞色素c氧化酶（10%）和NADH脱氢酶（13%）产生低水平抑制。谷氨酸脱氢酶也是LAC的作用靶点，1 mM LAC可抑制其85%的活性。循环伏安法数据表明，在当前实验条件下，LAC以及ISO均不发生氧化还原反应。LAC（0.05 - 0.75 mM）抑制了依赖谷氨酸氧化的肿胀，50%的抑制作用在0.5 mM LAC时出现。在LAC和ISO使用的所有浓度下，由KNO₃和缬氨霉素支持的肿胀也受到抑制，LAC的抑制作用强度较低，这表明内酯化对ISO结构的修饰减弱了其与膜的相互作用。这可能有助于减轻ISO对线粒体功能所描述的毒性作用，例如对呼吸链酶复合物和磷酸化活性的影响。
