Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, is a well-known herb with hepatotoxicity, and the biochemical mechanisms of the toxic action remain unknown. Diosbulbin B (DSB), a major component of DBL, can induce severer liver injury which requires cytochrome P450-catalyzed oxidation of the furan ring. It is reported that a cis-enedial reactive intermediate resulting from metabolic activation of DSB can react with thiols and amines to form pyrrole or pyrroline derivatives. In this study, we investigated the interaction of the reactive intermediate with polyamines, biogenic amines, and amino acids involved in the polyamine metabolic pathway, including putrescine, spermidine, spermine, histamine, arginine, ornithine, lysine, glutamine, and asparagine. Seven DSB-derived amine adducts were detected in microsomal incubations supplemented with DSB and individual amines. Six adducts were observed in cultured rat primary hepatocytes after exposure to DSB. DSB was found to induce apoptosis and cell death in time- and concentration-dependent manners. Apparently, the observed apoptosis was associated with the detected amine adduction. The findings facilitate the understanding of the mechanisms of toxic action of DSB.

中文翻译：

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薯，B代谢活化导致多胺，生物胺和氨基酸加成的证据。

薯（Dioscorea bulbifera L.，DBL）是一种具有肝毒性的著名草药，其毒性作用的生化机制尚不清楚。Diosbulbin B（DSB）是DBL的主要成分，可引起严重的肝损伤，这需要细胞色素P450催化的呋喃环氧化。据悉，一种顺式DSB代谢活化产生的烯键式反应性中间体可与硫醇和胺反应形成吡咯或吡咯啉衍生物。在这项研究中，我们调查了反应性中间体与多胺，生物胺和参与多胺代谢途径的氨基酸（包括腐胺，亚精胺，精胺，组胺，精氨酸，鸟氨酸，赖氨酸，谷氨酰胺和天冬酰胺）的相互作用。在补充了DSB和单个胺的微粒体培养物中检测到7种DSB衍生的胺加合物。暴露于DSB后，在培养的大鼠原代肝细胞中观察到6个加合物。发现DSB以时间和浓度依赖性方式诱导凋亡和细胞死亡。显然，观察到的细胞凋亡与检测到的胺加合有关。