Expressions of genes encoding drug-metabolizing enzymes are altered aftersevoflurane, isoflurane, propofol or dexmedetomidine anesthesia

摘要

We previously showed that sevoflurane anesthesia affected the expression ratios of 177 of 10,000genes in multiple organs of rats by microarray analyses. The maximum number of altered geneswas detected in the liver, and included several genes characterized as encoding drug-metabolizingenzymes (DMEs). Here, we investigated whether alterations of pharmacokinetic gene expressionsafter anesthesia differed between inhalation and intravenous anesthesia, and how long the altera-tions persisted after awakening from anesthesia. Livers were obtained from rats (n = 6 per group)anesthetized with sevoflurane, isoflurane, propofol or dexmedetomidine for 0 or 6 h, and ratsawakened for 24 h after anesthesia for 6 h. The mRNA expression ratios of eight genes encodingDMEs that showed the greatest alterations in the previous study, namely Cyp7al, Cyp2b15, Por,Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2, were measured by quantitative real-time reverse tran-scriptase-polymerase chain reaction. The expression ratios were mostly increased after 6 h of anes-thesia and returned to their control levels at 24 h after awakening from anesthesia. However, theexpression ratios of some genes remained elevated for 24 h after awakening from anesthesia.There were differences between inhalation and intravenous anesthesia, and interestingly, betweensevoflurane and isoflurane and between propofol and dexmedetomidine.