Babany G, Descatoire V, Corbic M, Gendre S, Degott C, Larrey D, Letteron P, Wandscheer J C, Funck-Brentano C, Pessayre D
Biochem Pharmacol. 1985 Feb 1;34(3):311-20. doi: 10.1016/0006-2952(85)90037-1.
The possibility of a relationship between hepatic and renal cytochrome P-450 contents was assessed in rats with liver disease. In rats killed 3 days after two-thirds hepatectomy (a model for hepatocellular insufficiency), the total microsomal cytochrome P-450 content of the whole liver was decreased by 60% as compared to that in control rats; renal cytochrome P-450 was increased by 30% while the 7-ethoxycoumarin deethylase activity of kidney microsomes was increased by 80%. In rats killed 7 days after bile duct ligation (a model for cholestasis) or 35 days after bile duct ligation (a model for biliary cirrhosis), hepatic cytochrome P-450 was decreased by 60% and 45%, respectively, while renal cytochrome P-450 content was increased by 50% and 150%, respectively. In contrast, in rats killed 15 days after the last dose of carbon tetrachloride, 1.3 ml/kg twice weekly for 3 months (a model for post-necrotic cirrhosis), both hepatic and renal cytochrome P-450 contents remained unchanged. Phenobarbital (80 mg/kg daily for 3 days) was a poor inducer of renal cytochrome P-450 in sham-operated rats but became a potent inducer of renal cytochrome P-450 in rats with two-thirds hepatectomy. We conclude that renal cytochrome P-450 is increased in three models in which hepatic cytochrome P-450 contents are decreased (two-thirds hepatectomy, cholestasis and biliary cirrhosis), but remains unchanged in a model of severe liver pathology, in which hepatic cytochrome P-450 content is not modified (late, post-necrotic cirrhosis). The hypothetical role of endogenous inducer(s) is discussed.
在患有肝脏疾病的大鼠中评估了肝脏和肾脏细胞色素P-450含量之间的关系。在三分之二肝切除术后3天处死的大鼠（肝细胞功能不全模型）中，与对照大鼠相比，全肝的微粒体细胞色素P-450总含量降低了60%；肾脏细胞色素P-450增加了30%，而肾微粒体的7-乙氧基香豆素脱乙基酶活性增加了80%。在胆管结扎术后7天处死的大鼠（胆汁淤积模型）或胆管结扎术后35天处死的大鼠（胆汁性肝硬化模型）中，肝脏细胞色素P-450分别降低了60%和45%，而肾脏细胞色素P-450含量分别增加了50%和150%。相比之下，在末次给予四氯化碳（1.3 ml/kg，每周两次，共3个月）后15天处死的大鼠（坏死后肝硬化模型）中，肝脏和肾脏细胞色素P-450含量均保持不变。苯巴比妥（80 mg/kg，每日一次，共3天）在假手术大鼠中对肾脏细胞色素P-450的诱导作用较弱，但在三分之二肝切除的大鼠中成为肾脏细胞色素P-450的强效诱导剂。我们得出结论，在肝脏细胞色素P-450含量降低的三种模型（三分之二肝切除、胆汁淤积和胆汁性肝硬化）中，肾脏细胞色素P-450增加，但在严重肝脏病理模型（晚期坏死后肝硬化，其中肝脏细胞色素P-450含量未改变）中保持不变。讨论了内源性诱导剂的假设作用。
