Hepatic metabolism and pulmonary toxicity of monocrotaline using isolated perfused liver and lung.
Hepatic metabolism and pulmonary toxicity of monocrotaline using isolated perfused liver and lung.
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DOI：
10.1016/0006-2952(84)90721-4
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发表时间：
1984-08
影响因子：
5.8
通讯作者：
W. Lafranconi;R. Huxtable
中科院分区：
文献类型：
--
作者：
W. Lafranconi;R. Huxtable
野百合碱是从猪屎豆种子中提取的吡咯里西啶生物碱。当通过离体肝脏灌注时，野百合碱代谢为埃利希反应性（E+）代谢物。野百合碱的代谢速度快，从雄性大鼠的肝脏比雌性大鼠，诱导苯巴比妥预处理，并抑制与P-450多功能氧化酶抑制剂SKF-525 A，缺氧灌注条件下，和低温共灌注。当由离体肝脏产生的代谢物以再循环方式通过离体肺灌注时，肺内皮的5-羟色胺转运与灌注介质中所含的E+物质的量相关。当肝脏代谢的野百合碱与SKF-525 A，低温灌注或缺氧条件下，肺内皮细胞的5-羟色胺转运抑制与对照组无变化。单用野百合碱对肺无影响。因此，离体灌注肝脏代谢野百合碱的化学物种，产生肺damagein体外。这提供了直接证据，表明肝脏代谢物可引起野百合碱体内肺毒性作用之一。
Monocrotaline is a pyrrolizidine alkaloid obtained from the seeds ofCrotalaria spectabilis. When perfused through an isolated liver, monocrotaline is metabolized to Ehrlich reactive (E+) metabolites. Metabolism of monocrotaline was faster in livers from male rats than female rats, was inducible with phenobarbital pretreatment, and was inhibited by coperfusion with the P-450 mixed-function oxidase inhibitor SKF-525A, anoxic perfusion conditions, and low temperatures. When metabolites generated by an isolated liver were perfused through isolated lungs in a recirculatory manner, serotonin transport by the pulmonary endothelium was reduced in correlation with the amount of E+ material contained in the perfusion medium. When metabolism of monocrotaline by the liver was inhibited with SKF-525A, low temperature perfusions or anoxic conditions, serotonin transport by the pulmonary endothelium was unchanged from controls. Monocrotaline alone had no effect on the lung. Thus, isolated perfused livers metabolized monocrotaline to chemical species which produced pulmonary damagein vitro. This provides direct evidence that liver metabolites can cause one of the pneumotoxic effects of monocrotaline observedin vivo.