Borlakoglu J T, Scott A, Henderson C J, Wolf C R
University of Reading, Department of Biochemistry and Physiology, U.K.
Biochem Pharmacol. 1993 Jul 6;46(1):29-36. doi: 10.1016/0006-2952(93)90344-v.
The hepatic microsomal drug metabolism during pregnancy and lactation was studied. Four days post partum, the concentrations of cytochrome P450 and cytochrome b5 were reduced by 50% when compared with pregnant rats, at day 10 of gestation. Within this time period the N-demethylation of aminopyrine, the rate of aldrin epoxidation and the N-demethylation of demethylnitrosamine was reduced by 53, 74 and 21%, respectively. However, the rates of ethoxyresorufin-O-deethylation did not differ amongst both groups and the deethylation of 4-nitroanisole and the 4-hydroxylation of aniline was increased by 71 and 31%, respectively in lactating rats. Furthermore, the activities of UDP-glucuronyltransferase and glutathione S-transferase were increased by 21 and 27%, but those of epoxide hydrolase were reduced by 85%. Western immunoblot analysis of microsomal proteins obtained from pregnant and lactating rats shows that only proteins encoded by the genes of CYP2C6 and CYP3A1 are expressed at detectable levels, whereas the expression of CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1 and CYP4A1 was not detectable in pregnant and lactating rats at a protein loading of 3 micrograms total protein per well. In contrast, in northern blot hybridization experiments, detectable amounts of mRNA of the above named isoenzymes were measurable, but at varying intensities. Based on the northern blot hybridization analysis, an approximate 4-fold and 3-fold increase in CYP2A1 mRNA and CYP3A1 mRNA was found, when lactating rats were compared with female controls or pregnant rats, at day 10 of gestation.
对妊娠和哺乳期的肝脏微粒体药物代谢进行了研究。产后四天，与妊娠第10天的大鼠相比，细胞色素P450和细胞色素b5的浓度降低了50%。在此时间段内，氨基比林的N-去甲基化、艾氏剂环氧化速率和去甲基亚硝胺的N-去甲基化分别降低了53%、74%和21%。然而，两组间乙氧异吩唑酮-O-脱乙基化速率没有差异，哺乳期大鼠中4-硝基苯甲醚的脱乙基化和苯胺的4-羟基化分别增加了71%和31%。此外，尿苷二磷酸葡萄糖醛酸基转移酶和谷胱甘肽S-转移酶的活性分别增加了21%和27%，但环氧化物水解酶的活性降低了85%。对妊娠和哺乳期大鼠获得的微粒体蛋白进行的蛋白质免疫印迹分析表明，只有CYP2C6和CYP3A1基因编码的蛋白在可检测水平表达，而在每孔总蛋白上样量为3微克时，妊娠和哺乳期大鼠中未检测到CYP1A1、CYP1A2、CYP2A1、CYP2B1、CYP2E1和CYP4A1的表达。相反，在Northern印迹杂交实验中，可检测到上述同工酶的mRNA量，但强度不同。基于Northern印迹杂交分析，与雌性对照或妊娠第10天大鼠相比，哺乳期大鼠的CYP2A1 mRNA和CYP3A1 mRNA分别增加了约4倍和3倍。
