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GENERAL ARTICLES

The Effects of Pentobarbital, Isoflurane, and Propofol on Immediate-Early Gene Expression in the Vital Organs of the Rat

Yoshihiro Hamaya, MD^*, Tomoo Takeda, MD^*, Shuji Dohi, MD^*, Shigeru Nakashima, MD, and Yoshinori Nozawa, MD

Departments of *Anesthesiology and Critical Care Medicine and Biochemistry, Gifu University School of Medicine, Gifu, Japan

Address correspondence and reprint requests to Dr. S. Dohi, Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, 40 Tsukasamachi, Gifu City, Gifu 500, Japan. Address e-mail to shu-dohi{at}cc.gifu-u.ac.jp

General anesthetics are known to transiently increase the expression of messenger ribonucleic acids (mRNAs) of immediate-early genes in the brain. We investigated whether the expression of two immediate-early genes in vital organs were modulated by various anesthetics. Inhaled isoflurane (n = 20), intraperitoneal pentobarbital (n = 20), and IV propofol (n = 20) were administered to male Sprague-Dawley rats, and five from each group were decapitated at 5, 30, 60, or 120 min after the induction of anesthesia. Control, nonanesthetized rats (n = 5) were handled gently and then decapitated. Reverse transcriptase-polymerase chain reactions were performed on total RNA from samples of the brain, heart, liver, and kidney to detect the expressions of c-fos and c-jun mRNAs. As internal control, cyclophilin mRNA was amplified simultaneously. The products were separated by electrophoresis, and the optical density of the bands was quantified. The expression of c-fos mRNA was transiently increased in the brain, and more strikingly and for longer times, in the kidney with all three anesthetics; the expression of c-fos mRNA was decreased in the heart with isoflurane and pentobarbital and increased in the liver with isoflurane and propofol. The expression of c-jun mRNA was increased in the heart, liver, and kidney with isoflurane, increased in the heart and kidney with pentobarbital, increased in the heart, liver, and kidney with propofol, and decreased in the brain with pentobarbital. Our results suggest that the appropriate anesthetics to be used to anesthetize animals differ in accord with the target organs in which the expressions of immediate-early genes in response to stimuli were studied.

Implications: In this study, there were quantitative and qualitative interanesthetic and interorgan differences in the expression of immediate-early genes, showing that general anesthetics can stimulate, rather than suppress, some intracellular events. Our results suggest that the appropriate anesthetics to be used to anesthetize animals differ in accord with the target organs in which the expressions of immediate-early genes in response to stimuli were studied.

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