Effect of oxygen concentration on the reaction of halothane with cytochrome P450 in liver microsomes and isolated perfused rat liver |
| |
| Authors: | Wolfgang Nastainczyk Volker Ullrich Helmut Sies |
| |
| Affiliation: | Department of Physiological Chemistry, University of the Saarland, Homburg-Saar, GFR Germany;Department of Physiological Chemistry, Physical Biochemistry and Cell Biology, University of Munich, Munich, GFR Germany |
| |
| Abstract: | The influence of oxygen on the complex formation of reduced cytochrome P450 with halothane has been investigated with liver microsomes and perfused livers from phenobarbital-pretreated rats. The reductive formation of the trifluoro carbene complex from halothane in liver microsomes was inhibited at high oxygen concentrations but started to appear below 50 μM oxygen and was maximal under anaerobic conditions. Metyrapone was an efficient inhibitor of the carbene complex formation. Organ spectrophotometry of isolated perfused livers established that the complex appeared already under slightly hypoxic conditions and that metyrapone addition to the perfusion medium abolished its formation. The results indicate the possibility of a reductive in vivo-metabolism of halothane to reactive intermediates when the oxygen concentration of the cell becomes lower than about 50 μM. |
| |
| Keywords: | Reprint requests should be sent to the following address: Physiologisch-chemisches Institut 665 HomburgSaar GFR Germany. |
| 本文献已被 ScienceDirect 等数据库收录！ |
