Metabolism of aqueous soluble nitroxides in hepatocytes: effects of cell integrity, oxygen, and structure of nitroxides.
Metabolism of aqueous soluble nitroxides in hepatocytes: effects of cell integrity, oxygen, and structure of nitroxides.
复制标题
肝细胞中水溶性氮氧化合物的代谢：细胞完整性、氧气和氮氧化合物结构的影响。
DOI：
10.1016/0304-4165(89)90033-0
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Swartz,HM
中科院分区：
文献类型：
--
作者：
Iannone,A;Hu,HP;Tomasi,A;Vannini,V;Swartz,HM
在可行的生物系统，包括活的动物，氮氧化物的最佳使用，需要通过主要器官系统，特别是肝脏的氮氧化物代谢的知识。我们在这里报告的细节代谢的几个原型水溶性氮氧自由基在新鲜分离的肝细胞悬浮液。代谢的一般模式与在其他类型的细胞中观察到的相似（以前的研究主要是在来自组织培养的细胞，如CHO细胞中进行的），包括还原成羟胺的主要初始反应，低氧细胞中某些氮氧化合物的代谢速率增加，与五元吡咯烷环相比，六元哌啶环上氮氧化合物的还原速率更快，并且大多数代谢是在细胞内进行的。肝细胞中的代谢与其他细胞系的不同之处在于：（1）由于受损肝细胞释放的抗坏血酸盐，细胞外介质显著减少;（2）由于亚细胞器受损，冻融细胞中的代谢速率降低。这些结果提供了许多所需的数据，以了解肝脏中的作用，氮氧化物的代谢由完整的动物和解释一些以前令人困惑的结果，这表明一个明显的异常高的代谢率的带电的氮氧化物（Cat 1）的肝细胞。我们的研究结果还表明，使用新鲜分离的细胞或组织匀浆可能会引入实验文物的研究中的氮氧化物的代谢。
The optimum use of nitroxides in viable biological systems, including live animals, requires knowledge of the metabolism of nitroxides by major organ systems, especially the liver. We report here details of the metabolism of several prototypic aqueous soluble nitroxides in suspensions of freshly isolated hepatocytes. The general patterns of metabolism were similar to those observed in other types of cells (previous studies have been done principally in cells from tissue culture, such as CHO cells) including the primary initial reaction being reduction to the hydroxylamine, an increased rate of metabolism of some nitroxides in hypoxic cells, faster rates of reduction of nitroxides on six-membered piperidine rings compared to five-membered pyrrolidine rings, and most metabolism being intracellular. Metabolism in hepatocytes differed from other cell lines in having (1) significant reduction in the extracellular medium due to ascorbate that was released from damaged hepatocytes; (2) decreased rates of metabolism in freeze-thawed cells due to damage to subcellular organelles. These results provide much of the data needed to understand the role of the liver in the metabolism of nitroxides by intact animals and explain some previously puzzling results which indicated an apparent unusually high rate of metabolism of a charged nitroxide (Cat1) by hepatocytes. Our results also indicate that the use of freshly isolated cells or tissue homogenates may introduce experimental artifacts in the study of the metabolism of nitroxides.