Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid.
Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid.
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发表时间：
1992-10
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通讯作者：
H. Sakai;T. Okamoto;Y. Kikkawa
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作者：
H. Sakai;T. Okamoto;Y. Kikkawa
自从发现干扰素诱导剂抑制肝脏药物代谢以来，细胞色素P450 （P450）的抑制作用已被证明与干扰素α / β和干扰素γ等细胞因子以及白细胞介素-1和肿瘤坏死因子共享。由于这些细胞因子是炎症介质，因此在乙型流感流行患者中报道茶碱毒性并不奇怪。因此，为了为类固醇和药物代谢改变的研究奠定基础，我们研究了多核糖苷酸：多核糖苷酸（poly I:poly C）给药后P450同工酶的改变。poly I:poly C给药24小时后，肝脏P450含量下降至对照组的57%，而其他微粒体酶的下降则不那么明显：P450还原酶（69%），细胞色素b5（74%）和nadh细胞色素b5还原酶（85%）。细胞色素P450 1A1、1A2、2C11和2E1 mRNA的抑制率超过对照组的60%。mRNA水平在72小时内未完全恢复。总的来说，mrna的变化与单加氧酶活性和P450同工酶含量的变化是平行的，这表明poly I:poly C对所有P450同工酶的影响都是翻译前的。poly I和poly c对P450同工酶没有明显的影响，这一研究补充了之前的报道，即细胞色素P450 2C11和3A2 mRNA下调。
Since the discovery that interferon inducers depress hepatic drug metabolism, the depressant action of cytochrome P450 (P450) has been demonstrated to be shared by cytokines such as interferon alpha/beta and interferon gamma as well as interleukin-1 and tumor necrosis factor. Because these cytokines are inflammatory mediators, it is not surprising that theophylline toxicity has been reported in patients with influenza B epidemic. Hence, to lay a foundation for studies of altered steroid and drug metabolism, the alteration of P450 isozymes was studied after polyriboinosinic acid:polyribocitidylic acid (poly I:poly C) administration. Twenty-four hours after poly I:poly C administration, hepatic P450 content decreased to 57% of control, whereas depression of other microsomal enzymes was less pronounced: P450 reductase (69%), cytochrome b5 (74%) and NADH-cytochrome b5 reductase (85%). The depression of mRNA for cytochrome P450 1A1, 1A2, 2C11 and 2E1 was more than 60% of the controls. Recovery of mRNA levels was not complete within 72 hr. The changes in mRNAs, in general, paralleled alterations of monooxygenase activities and P450 isozyme content suggesting that the effect of poly I:poly C is pretranslational for all P450 isozymes studied. No overt differential effect on P450 isozymes was found after an administration of poly I:poly C. This study complements the previous report which demonstrated down-regulation of mRNA for cytochrome P450 2C11 and 3A2.