Kawaji A, Isobe M, Tochino Y, Takabatake E, Chikaoka Y, Nomura Y, Tamura M
Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
Biochim Biophys Acta. 1998 Sep 16;1425(1):41-6. doi: 10.1016/s0304-4165(98)00069-5.
Benzydamine (BZY) N-oxidation mediated by flavin-containing monooxygenase (FMO) was evaluated in perfused brain and liver. Following 20 min of perfusion with modified Ringer solution, the infusion of BZY into brain or liver led to production of BZY N-oxide. BZY N-oxide, a metabolite of BZY oxidized exclusively by FMO, was mostly recovered in the effluent without undergoing further metabolism or reduction back to the parent substrate. The BZY N-oxide formation rate increased as the infusion concentration of BZY increased both in perfused brain and perfused liver. BZY N-oxidation activities in perfused rat brain and liver were 4.2 nmol/g brain/min and 50 nmol/g liver/min, respectively, although the BZY N-oxidation activity in brain homogenates was one 4000th that in liver homogenates. This is the first study of FMO activity in brain in situ.
在灌注的脑和肝脏中评估了含黄素单加氧酶（FMO）介导的苄达明（BZY）N-氧化作用。在用改良林格溶液灌注20分钟后，将BZY注入脑或肝脏会导致生成BZY N-氧化物。BZY N-氧化物是仅由FMO氧化的BZY代谢产物，大部分在流出物中回收，未经历进一步代谢或还原为母体底物。随着灌注脑和灌注肝脏中BZY注入浓度的增加，BZY N-氧化物的形成速率也增加。灌注大鼠脑和肝脏中的BZY N-氧化活性分别为4.2 nmol/g脑/分钟和50 nmol/g肝脏/分钟，尽管脑匀浆中的BZY N-氧化活性是肝匀浆中的四千分之一。这是首次对原位脑FMO活性进行的研究。
