Relationship of membrane fluidity, chemoprotection, and the intrinsic toxicity of butylated hydroxytoluene.
Relationship of membrane fluidity, chemoprotection, and the intrinsic toxicity of butylated hydroxytoluene.
复制标题
膜流动性、化学保护和丁基羟基甲苯的内在毒性的关系。
DOI：
10.1016/0006-2952(91)90428-8
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发表时间：
1991
影响因子：
5.8
通讯作者：
Moldéus,P
中科院分区：
文献类型：
--
作者：
Shertzer,HG;Bannenberg,GL;Rundgren,M;Moldéus,P
在离体大鼠肝细胞中，许多化学物质引起的毒性可由抗氧化剂（如丁基羟基甲苯（BHT））引起。尽管BHT保护作用在低于约50 nmol/mg蛋白质的浓度下是明显的，但较高浓度表现出内在的浓度依赖性毒性，其涉及线粒体功能障碍。我们评估的可能性，化学保护和内在毒性可以解释一个共同的机制，涉及改变细胞膜的物理性质。在红细胞（RBC）渗透脆性试验中，低于60 nmol/mg蛋白质的BHT可防止渗透脆性;然而，较高浓度的BHT可增强渗透脆性，因此在135 nmol/mg时发生总渗透溶解。BHT介导的渗透脆性的改变与膜流动性的变化相关，通过疏水探针1，6-二苯基-1，3，5-己三烯的荧光偏振测定。保护渗透与流动性降低相关，而增强红细胞脆性与流动性增加相关。在大鼠肝细胞悬液中，高BHT浓度也使血浆和线粒体膜透化，导致酶渗漏，这些作用伴随着膜流动性增强。虽然其他机制可能是有效的，但膜流动性的改变似乎是在低浓度下观察到的化学保护作用和在较高浓度BHT下观察到的内在毒性的部分原因。
In isolated rat hepatocytes, many chemicals elicit toxicity which is inhibitable by antioxidants such as butylated hydroxytoluene (BHT). Although BHT protection is evident at concentrations of less than about 50 nmol/mg protein, higher concentrations exhibit intrinsic concentration-dependent toxicity, which involves mitochondrial dysfunction. We evaluated the possibility that both chemoprotection and intrinsic toxicity could be explained by a common mechanism involving alterations in the physical properties of cellular membranes. In the red blood cell (RBC) osmotic fragility assay, BHT at less than 60 nmol/mg protein protected against osmotic fragility; however, BHT at higher concentrations enhanced osmotic fragility such that total osmolysis occurred at 135 nmol/mg. The BHT-mediated alterations in osmotic fragility correlated with changes in membrane fluidity, determined by fluorescence polarization of the hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene. Protection from osmolysis correlated with decreased fluidity, while enhanced RBC fragility correlated with increased fluidity. In rat hepatocyte suspensions, high BHT concentrations also permeabilized the plasma and mitochondrial membranes to enzyme leakage, and these effects were accompanied by enhanced membrane fluidity. Although other mechanisms may be operative, alterations in membrane fluidity appear to be, in part, responsible for the observed chemoprotective effects at low concentrations, and intrinsic toxicity at higher concentrations of BHT.