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Toxicity of lupane derivatives on anionic membrane models, isolated rat mitochondria and selected human cell lines: Role of terminal alkyl chains
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-10-04 , DOI: 10.1016/j.cbi.2018.10.002
Filipa S. Carvalho , Catarina M. Morais , Jon Holy , Dmytro Krasutsky , Sergiy V. Yemets , Pavel A. Krasutsky , Amália S. Jurado , Paulo J. Oliveira , Teresa L. Serafim

Triterpenoids have multiple biological properties, although little information is available regarding their toxicity. The present study evaluates the toxicity of two new synthetic lupane derivatives using distinct biological models including synthetic lipids membranes, isolated liver and heart mitochondria fractions, and cell lines in culture. The two novel triterpenoids caused perturbations in the organization of synthetic lipid bilayers, leading to changes in membrane fluidity. Inhibition of cell proliferation and mitochondrial and nuclear morphological alterations were also identified. Inhibition of mitochondrial oxygen consumption, transmembrane electric potential depolarization and induction of the mitochondrial permeability transition pore was observed, although effects on isolated mitochondrial fractions were tissue-dependent (e.g. liver vs. heart).

The size and length of hydrocarbon chains in the two molecules appear to be determinant for the degree of interaction with mitochondria, especially in the whole cell environment, where more barriers for diffusion exist. The results suggest that the positively charged triterpenoids target mitochondria and disrupt bioenergetics.



中文翻译:

紫杉烷衍生物对阴离子膜模型,离体大鼠线粒体和部分人类细胞系的毒性:末端烷基链的作用

三萜类化合物具有多种生物学特性,尽管关于其毒性的信息很少。本研究使用不同的生物学模型(包括合成脂质膜,分离的肝和心脏线粒体级分以及培养的细胞系)评估两种新的合成卢烷衍生物的毒性。这两种新颖的三萜类化合物在合成脂质双层的组织中引起扰动,从而导致膜流动性的变化。还鉴定了抑制细胞增殖和线粒体以及核形态改变。观察到线粒体耗氧量的抑制,跨膜电位去极化和线粒体通透性过渡孔的诱导,尽管对分离的线粒体部分的影响是组织依赖性的(例如肝与肝)。

这两个分子中烃链的大小和长度似乎决定了与线粒体相互作用的程度,特别是在存在更多扩散障碍的整个细胞环境中。结果表明,带正电荷的三萜类化合物靶向线粒体并破坏生物能。

更新日期:2018-10-04
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