Mechanism of hepatic heme oxygenase-1 induction by isoflurane

被引：41

作者：

Hoetzel, A ^{[1
]}

Leitz, D ^{[1
]}

Schmidt, R ^{[1
]}

Tritschler, E ^{[1
]}

Bauer, I ^{[1
]}

Loop, T ^{[1
]}

Humar, M ^{[1
]}

Geiger, KK ^{[1
]}

Pannen, BHJ ^{[1
]}

机构：

[1] Univ Freiburg, Dept Anesthesiol & Crit Care Med, D-79106 Freiburg, Germany

来源：

ANESTHESIOLOGY | 2006年 / 104卷 / 01期

关键词：

D O I：

10.1097/00000542-200601000-00016

中图分类号：

R614 [麻醉学];

学科分类号：

100217 ;

摘要：

Background: The heme oxygenase pathway represents a major cell and organ protective system in the liver. The authors recently showed that isoflurane and sevoflurane up-regulate the inducible isoform heme oxygenase 1 (HO-1). Because the activating cascade remained unclear, it was the aim of this study to identify the underlying mechanism of this effect. Methods: Rats were anesthetized with pentobarbital intravenously or with isoflurane per inhalation (2-3 vol%). Kupffer cell function was inhibited by dexamethasone or gadolinium chloride. Nitric oxide synthases were inhibited by either N-omega-nitro-L-arginine methyl ester or S-methyl thiourea. N-Acetyl-cysteine served as an antioxidant, and diethyldithiocarbamate served as an inhibitor of cytochrome P450 2E1. Protein kinase C and phospholipase A. were inhibited by chelerythrine or quinacrine, respectively. HO-1 was analyzed in liver tissue by Northern blot, Western blot, immunostaining, and enzymatic activity assay. Results: In contrast to pentobarbital, isoflurane induced HO-1 after 4-6 h in hepatocytes in the pericentrat region of the liver. The induction was prevented in the presence of dexamethasone (P < 0.05) and gadolinium chloride (P < 0.05). inhibition of nitric oxide synthases or reactive oxygen intermediates did not affect isoflurane-mediated HO-1 up-regulation. In contrast, chelerythrine (P < 0.05) and quinacrine (P < 0.05) resulted in a blockade of HO-1 induction. Conclusion: The up-regulation of HO-1 by isollurane in the liver is restricted to parenchymal cells and depends on Kupffer cell function. The induction is independent of nitric oxide or reactive oxygen species but does involve protein kinase C and phospholipase A(2).

引用

页码：101 / 109

页数：9

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