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萜类化合物樟脑、蒎烯和侧柏酮的致卟啉特性(附对苦艾酒历史影响及文森特·梵高疾病的说明)

Porphyrogenic properties of the terpenes camphor, pinene, and thujone (with a note on historic implications for absinthe and the illness of Vincent van Gogh).

作者信息

Bonkovsky H L, Cable E E, Cable J W, Donohue S E, White E C, Greene Y J, Lambrecht R W, Srivastava K K, Arnold W N

机构信息

Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.

出版信息

Biochem Pharmacol. 1992 Jun 9;43(11):2359-68. doi: 10.1016/0006-2952(92)90314-9.

Abstract

Camphor, alpha-pinene (the major component of turpentine), and thujone (a constituent in the liqueur called absinthe) produced an increase in porphyrin production in primary cultures of chick embryo liver cells. In the presence of desferrioxamine (an iron chelator which inhibits heme synthesis and thereby mimics the effect of the block associated with acute porphyria), the terpenes enhanced porphyrin accumulation 5- to 20-fold. They also induced synthesis of the rate-controlling enzyme for the pathway, 5-aminolevulinic acid synthase, which was monitored both spectrophotometrically and immunochemically. These effects are shared by well-known porphyrogenic chemicals such as phenobarbital and glutethimide. Camphor and glutethimide alone led to the accumulation of mostly uro- and heptacarboxylporphyrins, whereas alpha-pinene and thujone resulted in lesser accumulations of porphyrins which were predominantly copro- and protoporphyrins. In the presence of desferrioxamine, plus any of the three terpenes, the major product that accumulated was protoporphyrin. The present results indicate that the terpenes tested are porphyrogenic and hazardous to patients with underlying defects in hepatic heme synthesis. There are also implications for the illness of Vincent van Gogh and the once popular, but now banned liqueur, called absinthe.

摘要

樟脑、α-蒎烯(松节油的主要成分)和侧柏酮(一种名为苦艾酒的利口酒中的成分)可使鸡胚肝细胞原代培养物中的卟啉生成增加。在去铁胺(一种抑制血红素合成从而模拟与急性卟啉症相关阻断效应的铁螯合剂)存在的情况下,这些萜类物质可使卟啉积累增加5至20倍。它们还诱导了该途径的限速酶5-氨基酮戊酸合酶的合成,这通过分光光度法和免疫化学法进行监测。这些效应与苯巴比妥和格鲁米特等著名的致卟啉化学物质相同。单独使用樟脑和格鲁米特会导致主要是尿卟啉和七羧基卟啉的积累,而α-蒎烯和侧柏酮导致的卟啉积累较少,主要是粪卟啉和原卟啉。在去铁胺以及三种萜类物质中的任何一种存在的情况下,积累的主要产物是原卟啉。目前的结果表明,所测试的萜类物质具有致卟啉性,对肝血红素合成存在潜在缺陷的患者有害。这也与文森特·梵高的疾病以及曾经流行但现在已被禁止的利口酒苦艾酒有关。

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