肺毒性是毒性吡咯利西啶类生物碱的常见现象。

IF 1.2 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES
Zijing Song, Yisheng He, Jiang Ma, Peter P Fu, Ge Lin
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引用次数: 15

摘要

肝毒性吡咯利西啶生物碱(PAs)在肝脏中被代谢激活,形成反应性脱氢PAs,产生吡咯蛋白加合物,导致肝毒性。与其他pa不同的是,Monocrotaline也具有肺毒性,这可能是由于肝脏产生的相应的脱氢pa迁移到肺中,形成吡咯蛋白加合物,从而诱发肺毒性。本研究调查了其他PAs是否也具有肺毒性。通过大鼠肝或肺S9孵育,研究了四种具有代表性的肝毒性PAs(单芥碱、反转录酶、riddelliine和clivorine)的代谢激活。所有PAs在大鼠肝脏S9中均显著产生吡咯蛋白加合物,但在肺S9中可忽略不计,表明肝脏是代谢激活产生脱氢PAs的关键器官。此外,以0.2 mmol/kg的相同肝毒性剂量口服大鼠,研究了这四种PA和另外两种PA存在于Gynura segetum生物碱提取物中。Gynura segetum是一种广泛使用的产生PA的草药,在中国导致人类PA中毒。所有6种PAs均在48 h内引起大鼠肺毒性。结果表明,肺毒性可能是PAs的一种普遍现象,肝脏来源的脱氢PAs可能转移到肺部并形成吡咯蛋白加合物,导致肺毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pulmonary toxicity is a common phenomenon of toxic pyrrolizidine alkaloids.

The hepatotoxic pyrrolizidine alkaloids (PAs) are metabolically activated in the liver to form reactive dehydro-PAs, which generate pyrrole-protein adducts leading to hepatotoxicity. Monocrotaline, but not other PAs, is also pneumotoxic, supposedly due to the migration of the liver-generated corresponding dehydro-PA into the lung to form pyrrole-protein adducts to induce pneumotoxicity. The present study investigated whether other PAs are also pneumotoxic. Metabolic activation of four representative hepatotoxic PAs, monocrotaline, retrorsine, riddelliine and clivorine, was investigated using rat liver or lung S9 incubation. All PAs produced pyrrole-protein adducts significantly in rat liver S9 but negligible in lung S9 fraction, revealing that liver is the key organ responsible for metabolic activation generating dehydro-PAs. Furthermore, these four PAs and another two PAs present in the alkaloid extract of Gynura segetum, a widely used PA-producing herb responsible for human PA poisonings in China, were orally administered to rats using the same hepatotoxic dose of 0.2 mmol/kg. All six PAs induced pneumotoxicity in rats within 48 h. The results demonstrated that pneumotoxicity could be a common phenomenon of PAs and the liver-derived dehydro-PAs might move to the lung and form pyrrole-protein adducts, leading to pulmonary toxicity.

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CiteScore
4.60
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