Drug-induced accumulation of uroporphyrin in chicken hepatocyte cultures. Structural requirements for the effect and role of exogenous iron.
Drug-induced accumulation of uroporphyrin in chicken hepatocyte cultures. Structural requirements for the effect and role of exogenous iron.
复制标题
鸡肝细胞培养物中药物诱导的尿卟啉积累。
作者：
A. Ferioli;C. Harvey;F. de Matteis
研究了药物在17日龄鸡胚肝细胞中引起尿卟啉症的能力，并将培养中细胞的反应与卵内胚胎完整肝脏的反应进行了比较。在这种鸡胚系统中，在19-24小时内引起尿卟啉积累的药物只能在培养物中进行;相反，2-烯丙基-2-异丙基乙酰胺和3，5-二乙氧羰基-1，4-二氢可力丁刺激原卟啉的产生，在培养物和卵中都有效。在肝细胞培养物中证明了外源性铁在恶化药物诱导的尿卟啉症中的作用;铁还导致在不存在卟啉化学物质的情况下从添加的5-氨基乙酰丙酸盐中优先积累尿卟啉。尿卟啉症是由不同结构的药物在肝细胞培养物中诱导的，这表明它们相互作用的主要分子靶点可能在其结合特性上相对非特异性。这些结果进行了简要讨论，并考虑了两种替代假设的药物诱导的影响，在尿卟啉原代谢。
The ability of drugs to cause uroporphyria in hepatocytes from 17-day-old chick embryos has been investigated and the response of the cells in culture compared with that of the intact liver of the embryos in ovo. In this chick-embryo system, drugs that cause accumulation of uroporphyrin within 19-24 h can only do so in culture; in contrast, 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which stimulate production of protoporphyrin, are effective both in culture and in ovo. A role of exogenous iron in worsening drug-induced uroporphyria was demonstrated in cultures of hepatocytes; iron also caused preferential accumulation of uroporphyrin from added 5-aminolaevulinate in the absence of a porphyrogenic chemical. Uroporphyria was induced in cultures of hepatocytes by drugs of widely different structures, suggesting that the primary molecular target with which they interact may be relatively aspecific in its binding characteristics. These results are briefly discussed, and two alternative hypotheses for the drug-induced effect in uroporphyrinogen metabolism are considered.