Mortensen B, Eide I, Zahlsen K, Nilsen O G
Section for Environmental Technology, Norsk Hydro ASA, Research Centre, Porsgrunn, Norway.
Arch Toxicol. 2000 Aug;74(6):308-12. doi: 10.1007/s002040000135.
In vitro rates of metabolism and Michaelis-Menten constants were determined for 25 different C6 to C10 hydrocarbons using rat liver slices in a vial head-space equilibration system. The rates of metabolism were compared with steady-state levels obtained in vivo in the same strains of rats after inhalation. Aromates were metabolized at a higher rate than naphthenes n-alkanes, isoalkanes and 1-alkenes. The aromates showed, in contrast to the other hydrocarbons investigated, increased metabolism with increasing number of carbon atoms up to C8 (o-xylene, the most extensively metabolized compound). The in vivo steady-state concentrations of the aromates in blood were inversely related to the in vitro efficiency of their metabolism. This explains the pattern of blood levels observed for the C6 to C10 aromates in the rat after inhalation, with o-xylene demonstrating the lowest concentration. In general, the extent of tissue metabolism of the investigated hydrocarbons might be of greater importance for their body distribution than their lipophilicity, especially for the highly metabolized compounds. The high in vitro intrinsic liver clearances found for the aromates indicate a flow-dependent metabolism of these hydrocarbons in vivo. The head-space liver slice equilibration system seems to work adequately for metabolic studies of hydrocarbons with different volatility and water solubility.
使用小瓶顶空平衡系统中的大鼠肝切片，测定了25种不同的C6至C10烃类化合物的体外代谢速率和米氏常数。将这些代谢速率与同一品系大鼠吸入后在体内获得的稳态水平进行了比较。芳烃的代谢速率高于环烷烃、正构烷烃、异烷烃和1-烯烃。与其他所研究的烃类化合物不同，芳烃在碳原子数增加至C8（邻二甲苯，代谢最广泛的化合物）时，代谢增加。芳烃在血液中的体内稳态浓度与它们体外代谢效率呈负相关。这解释了大鼠吸入后C6至C10芳烃在血液中观察到的水平模式，其中邻二甲苯浓度最低。一般来说，所研究烃类化合物的组织代谢程度对其体内分布的重要性可能大于其亲脂性，特别是对于高代谢化合物。芳烃在体外肝脏的高内在清除率表明这些烃类化合物在体内存在血流依赖性代谢。顶空肝切片平衡系统似乎适用于不同挥发性和水溶性烃类化合物的代谢研究。
