Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK.
Isoflurane has a pharmacological preconditioning effect against ischemia in the heart and brain, but whether this also occurs in the kidney is unclear. In this study, we investigated pharmacological preconditioning by isoflurane in the rat kidney. In the isoflurane preconditioning group (1.5% isoflurane for 20 min before renal ischemia) serum creatinine (1.2 +/- 0.7 and 1.1 +/- 0.2 mg/dL) and blood urea nitrogen (99 +/- 29 and 187 +/- 31 mg/dL) were significantly smaller at 24 and 48 h after reperfusion than in the nonpreconditioning group (creatinine; 2.4 +/- 1.2 and 2.9 +/- 0.9 mg/dL, urea; 62 +/- 19 and 79 +/- 20 mg/dL). We also investigated the intracellular signal transduction involved in isoflurane preconditioning in the kidney. The activities of the stress protein kinases, JNK and ERK but not p38, were significantly less in the kidneys of the preconditioning group than in those of the nonpreconditioning group (P < 0.05). We conclude that isoflurane has a preconditioning effect against renal ischemia/reperfusion injury when administered before ischemia. Inhibition of the protein kinases, JNK and ERK, might be involved in the mechanisms of isoflurane preconditioning.
Hashiguchi
Hideo
H
Department of Anesthesiology, Department of Histology, Nagasaki University School of Medicine, Nagasaki, Japan.
Morooka
Hiroaki
H
Miyoshi
Hiroshi
H
Matsumoto
Masanori
M
Koji
Takehiko
T
Sumikawa
Koji
K
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D007530:Isoflurane / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D018685:Anesthetics, Inhalation; D047428:Protein Kinase Inhibitors; D007530:Isoflurane; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases