Furukawa T, Manabe S, Ohashi Y, Sharyo S, Kimura K, Mori Y
Laboratory Animal Science and Toxicology Laboratories, Sankyo Co., Ltd., Shizuoka, Japan.
Toxicol Lett. 1999 Jul 30;108(1):11-6. doi: 10.1016/s0378-4274(99)00065-x.
It has been reported that drug metabolizing enzyme activities in the liver fluctuate daily, though the daily fluctuation of 7-alkoxycoumarin O-dealkylase (ACD) activities catalyzed by P450 has not been examined. The ACD activities are known to be useful to clarify the extensive induction of P450-dependent oxygenases. In the present study, the hepatic ACD activities, as well as P450 content, were investigated periodically in male F344 rats under ad libitum-feeding or fasting condition. The ACD activities in ad libitum-fed rats were found to follow obvious daily fluctuations with high values during dark periods and with low values during light periods. This agreed with the other previous results of drug metabolizing enzyme activities measured with other substrates. Because the daily fluctuation was also observed in fasted rats, the fluctuation in ACD activities was clearly not affected by feeding, an external factor. P450 content, however, showed different fluctuation patterns from the ACD activities. This suggests that the fluctuation of ACD activities might not be related to the quantitative variation of P450 proteins.
据报道，肝脏中的药物代谢酶活性每日都会波动，不过由细胞色素P450催化的7-烷氧基香豆素O-脱烷基酶（ACD）活性的每日波动情况尚未得到研究。已知ACD活性有助于阐明细胞色素P450依赖性加氧酶的广泛诱导作用。在本研究中，对随意进食或禁食条件下的雄性F344大鼠的肝脏ACD活性以及细胞色素P450含量进行了定期研究。结果发现，随意进食大鼠的ACD活性呈现明显的每日波动，黑暗期活性较高，光照期活性较低。这与之前用其他底物测定的药物代谢酶活性的结果一致。由于在禁食大鼠中也观察到了每日波动，所以ACD活性的波动显然不受进食这一外部因素的影响。然而，细胞色素P450含量呈现出与ACD活性不同的波动模式。这表明ACD活性的波动可能与细胞色素P450蛋白的定量变化无关。
