Synergistic increases in rat hepatic cytochrome P450s by ethanol and isopentanol.
Synergistic increases in rat hepatic cytochrome P450s by ethanol and isopentanol.
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乙醇和异戊醇协同增加大鼠肝细胞色素 P450。
DOI：
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发表时间：
1994
影响因子：
3.5
通讯作者：
J. Sinclair
中科院分区：
文献类型：
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作者：
C. A. Louis;S. Wood;V. Kostrubsky;P. Sinclair;J. Sinclair
本研究的目的是确定异戊醇单独或与乙醇合用是否会增加大鼠肝脏中的细胞色素P4502/2、细胞色素P450 E或细胞色素P3A的含量。在Lieber-DeCarli液体饲料中加入递增剂量的异戊醇(0.5%、1%、2%或3%)和5.6%的乙醇，连续7天。单独给予0.5%或3%的异戊醇。单独使用异戊醇后，细胞色素P450 2/2和细胞色素P3A的表达略有增加。然而，当异戊醇(2%或3%)与乙醇联合使用时，观察到P4502B1/2的协同增加。联合酒精治疗也导致免疫活性细胞色素P3A的增加比单独酒精治疗更大。仅乙醇一项就可使细胞色素P450 2E增加5倍。在乙醇中加入异戊醇，会导致细胞色素P450酶2 E小幅增加或没有增加。这些结果证实了我们以前在培养肝细胞中的发现，当异戊醇与乙醇联合使用时，细胞色素P4502/2的表达协同增加。乙醇以及乙醇与异戊醇联合使用时，细胞色素P450 2/2、细胞色素P4E和细胞色素P3A蛋白含量的增加与其mRNAs的增加有关。与单独服用3%异戊醇的大鼠相比，服用3%异戊醇和乙醇的大鼠的血液中异戊醇水平高出10倍。根据这些结果，我们认为异戊醇，酒精饮料中的一种高级链醇，可以促进酒精饮料消费后观察到的肝脏细胞色素P450的增加。
The purpose of this study was to determine if isopentanol alone or in combination with ethanol increased CYP2B1/2, CYP2E or CYP3A in the livers of rats. Increasing doses of isopentanol (0.5, 1, 2 or 3%) were administered in combination with 5.6% ethanol in the Lieber-DeCarli liquid diet for 7 days. Doses of 0.5 or 3% isopentanol were also administered alone. Isopentanol alone caused small increases in CYP2B1/2 and CYP3A. However, when isopentanol (2 or 3%) was combined with ethanol a synergistic increase in P4502B1/2 was observed. The combined alcohol treatment also resulted in a greater increase in immunoreactive CYP3A than either alcohol alone. Ethanol alone increased CYP2E 5-fold. Inclusion of isopentanol with ethanol resulted in either small or no additional increases in CYP2E. These results confirm our previous findings in cultured hepatocytes that when isopentanol is combined with ethanol, there is a synergistic increase in CYP2B1/2. Increases in CYP2B1/2, CYP2E and CYP3A protein moieties by ethanol, and by ethanol in combination with isopentanol, were associated with increases in their mRNAs. Blood isopentanol levels were 10-fold greater in rats administered 3% isopentanol in combination with ethanol compared to rats administered 3% isopentanol alone. From these results we suggest that isopentanol, a higher chain alcohol in alcoholic beverages, can contribute to increases in hepatic cytochrome P450 observed following consumption of alcoholic beverages.