Bonkowsky H L, Healey J F, Sinclair P R, Mayer Y P, Erny R
Biochem J. 1980 May 15;188(2):289-95. doi: 10.1042/bj1880289.
We have studied effects of single doses of 2-allyl-2-isopropylacetamide and ferric citrate on hepatic haem turnover in rats. Haem was pre-labelled by intraperitoneal administration of 5-amino-[4-(14)C]laevulinate 4h before other treatments. Computer-assisted analysis of the haem decay curve showed that at least two exponential components were involved implying two haem pools. In control rats the size of the rapidly-turning-over pool was 38% of the total. Treatment with 2-allyl-2-isopropylacetamide alone resulted in a 2.3-fold increase in the fractional size of this pool. Treatment with ferric citrate alone increased the size of this pool 1.8-fold; treatment with both agents together had no measurable effect beyond that produced by 2-allyl-2-isopropylacetamide. The apparent rate constant for disappearance of labelled haem from the first pool was not affected by treatment with 2-allyl-2-isopropylacetamide or ferric citrate, indicating that these treatments affect hepatic haem turnover primarily by altering the distribution of haem synthesized in the liver. The increased haem degradation after treatment with 2-allyl-2-isopropylacetamide alone was associated with the accumulation of ;green pigments' in the liver. These pigments were detectable 1.5h after drug treatment; their total amount increased steadily for 28h and then declined. Despite this increase in amount, radioactivity of the ;green pigment' fraction fell rapidly in a biphasic fashion. Some of the radioactivity that initially was found in the ;green pigment' fraction was later found in an aqueous fraction, not extractable by acidic ethyl acetate. Rats given ferric citrate together with 2-allyl-2-isopropylacetamide accumulated less ;green pigments'.
我们研究了单剂量的2-烯丙基-2-异丙基乙酰胺和柠檬酸铁对大鼠肝脏血红素周转的影响。在进行其他处理前4小时，通过腹腔注射5-氨基-[4-(14)C]乙酰丙酸对血红素进行预标记。对血红素衰变曲线进行计算机辅助分析表明，至少有两个指数成分，这意味着存在两个血红素池。在对照大鼠中，快速周转池的大小占总量的38%。单独用2-烯丙基-2-异丙基乙酰胺处理导致该池的分数大小增加了2.3倍。单独用柠檬酸铁处理使该池的大小增加了1.8倍；两种药物一起处理产生的效果与单独用2-烯丙基-2-异丙基乙酰胺处理相比，没有可测量的额外影响。标记血红素从第一个池中消失的表观速率常数不受2-烯丙基-2-异丙基乙酰胺或柠檬酸铁处理的影响，这表明这些处理主要通过改变肝脏中合成的血红素的分布来影响肝脏血红素周转。单独用2-烯丙基-2-异丙基乙酰胺处理后血红素降解增加与肝脏中“绿色色素”的积累有关。在药物处理后1.5小时可检测到这些色素；它们的总量在28小时内稳步增加，然后下降。尽管数量增加，但“绿色色素”部分的放射性以双相方式迅速下降。最初在“绿色色素”部分发现的一些放射性后来在一个水相中被发现，该水相不能被酸性乙酸乙酯萃取。同时给予柠檬酸铁和2-烯丙基-2-异丙基乙酰胺的大鼠积累的“绿色色素”较少。
