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

Abstract

We previously showed that sevoflurane anesthesia affected the expression ratios of 177 of 10,000 genes in multiple organs of rats by microarray analyses. The maximum number of altered genes was detected in the liver, and included several genes characterized as encoding drug-metabolizing enzymes (DMEs). Here, we investigated whether alterations of pharmacokinetic gene expressions after anesthesia differed between inhalation and intravenous anesthesia, and how long the alterations 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 rats awakened for 24 h after anesthesia for 6 h. The mRNA expression ratios of eight genes encoding DMEs that showed the greatest alterations in the previous study, namely Cyp7a1, Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2, were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression ratios were mostly increased after 6 h of anesthesia and returned to their control levels at 24 h after awakening from anesthesia. However, the expression ratios of some genes remained elevated for 24 h after awakening from anesthesia. There were differences between inhalation and intravenous anesthesia, and interestingly, between sevoflurane and isoflurane and between propofol and dexmedetomidine.

Propofol anaesthesia alters the cerebral proteome differently from sevoflurane anaesthesia

“…For instance, we found persistent suppression of the expression of several genes implicated in circadian rhythms (e.g., Per2, Dbp, Egr1, Krox20 and NGF1-B) following treatment of rats with sevoflurane (20) and propofol or dexmedetomidine (41). We have also reported changes in the expression of drug metabolising enzymes in rats (e.g., Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2) in response to sevoflurane, isoflurane, propofol, or dexmedetomidine anaesthesia (30,37) The observed changes varied depending on the identity of the anaesthetic used, and also on the mode of administration (inhaled vs. intravenous). Therefore, it is clear that anaesthetics have significant effects on the genomic expression of important regulatory nasia) was obtained from the Animal Experimental Ethical Review Committee of Nippon Medical School (review number: 22-085).…”

Volatile and Intravenous Anesthesia Alter Rat Liver Proteins: Proteomic Time Course Analysis of Rat Liver Proteins

“…Propofol is an alkylphenol formulated in a liquid emulsion and metabolized in the liver. We chose the administration durations and the times for taking samples based on our previous studies [19,25,39]; however, liquid emulsion itself may affect lipid profiles during or after propofol anesthesia. In clinical situations, propofol is usually injected with a lipid emulsion.…”

Regulation of hepatic ABCC transporters by xenobiotics and in disease states

“…Mrp2 mRNA expression returns to the control values at 24 hours after awakening from anesthesia by sevoflurane, propofol, or dexmedetomidine. By contrast, liver Mrp2 increases significantly in rats receiving isoflurane and does not return to normal levels 24 hours after awakening from anesthesia (Nakazato et al, 2009). …”