ALTERATIONS IN RAT HEPATIC DRUG-METABOLISM DURING PREGNANCY AND LACTATION
ALTERATIONS IN RAT HEPATIC DRUG-METABOLISM DURING PREGNANCY AND LACTATION
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DOI：
10.1016/0006-2952(93)90344-v
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发表时间：
1993-07-06
影响因子：
5.8
通讯作者：
WOLF, CR
中科院分区：
文献类型：
--
作者：
BORLAKOGLU, JT;SCOTT, A;WOLF, CR
研究了妊娠和哺乳期肝微粒体药物代谢。产后4 d，与妊娠第10天相比，细胞色素P450和细胞色素b5的浓度降低了50%。在这段时间内，氨基吡啶的n -去甲基化、艾氏醇环氧化和去甲基亚硝胺的n -去甲基化分别降低了53%、74%和21%。然而，在哺乳期大鼠中，乙氧基间苯甲醚- o -去乙基化率在两组之间没有差异，4-硝基苯胺的去乙基化和苯胺的4-羟基化分别增加了71%和31%。udp -葡萄糖醛基转移酶和谷胱甘肽s -转移酶活性分别提高了21%和27%，而环氧化物水解酶活性降低了85%。Western免疫印迹分析妊娠和哺乳期大鼠的微体蛋白，发现只有CYP2C6和CYP3A1基因编码的蛋白在可检测水平上表达，而在每孔蛋白总蛋白为3杯时，妊娠和哺乳期大鼠的CYP1A1、CYP1A2、CYP2A1、CYP2B1、CYP2E1和CYP4A1均未检测到表达。相比之下，在northern blot杂交实验中，上述命名的同工酶的mRNA的可检测量是可测量的，但强度不同。根据northern blot杂交分析，在妊娠第10天，与雌性对照或妊娠大鼠相比，泌乳大鼠CYP2A1 mRNA和CYP3A1 mRNA分别增加了约4倍和3倍。
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 mug 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.