Expressions of genes encoding drug-metabolizing enzymes are altered after sevoflurane, isoflurane, propofol or dexmedetomidine anesthesia.
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.
Nakazato
Keiko
K
Department of Anesthesiology, Nippon Medical School, Tokyo, Japan. k-nakazato@nms.ac.jp
Yoshida
Yuko
Y
Takemori
Ken
K
Kobayashi
Katsuya
K
Sakamoto
Atsuhiro
A
D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013997:Time Factors
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D000077149:Sevoflurane; D020927:Dexmedetomidine; D007530:Isoflurane; D015742:Propofol