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Anti-inflammatory and antinecrotic effects of the volatile anesthetic sevoflurane in kidney proximal tubule cells

Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York

Submitted 19 October 2005 ; accepted in final form 7 February 2006

Renal ischemia-reperfusion (IR) injury is a major clinical problem without effective therapy. We recently reported that volatile anesthetics protect against renal IR injury, in part, via their anti-inflammatory properties. In this study, we demonstrate the anti-inflammatory and antinecrotic effects of sevoflurane in cultured kidney proximal tubule cells and probed the mechanisms of sevoflurane-induced renal cellular protection. To mimic inflammation, human kidney proximal tubule (HK-2) cells were treated with tumor necrosis factor- (TNF-; 25 ng/ml) in the presence or absence of sevoflurane. In addition, we studied the effects of sevoflurane pretreatment on hydrogen peroxide (H₂O₂)-induced necrotic cell death in HK-2 or porcine proximal tubule (LLC-PK₁) cells. We demonstrate that sevoflurane suppressed proinflammatory effects of TNF- evidenced by attenuated upregulation of proinflammatory cytokine mRNA (TNF-, MCP-1) and ICAM-1 protein and reduced nuclear translocation of the proinflammatory transcription factors NF-B and AP-1. Sevoflurane reduced necrotic cell death induced with H₂O₂ in HK-2 cells as well as in LLC-PK₁ cells. Sevoflurane treatment resulted in phosphorylation of prosurvival kinases, ERK and Akt, and increased de novo HSP-70 protein synthesis without affecting the synthesis of HSP-27 or HSP-32. We conclude that sevoflurane has direct anti-inflammatory and antinecrotic effects in vitro in a renal cell type particularly sensitive to injury following IR injury. These mechanisms may, in part, account for volatile anesthetics' protective effects against renal IR injury.

acute renal failure; HK-2 cells; inflammation; necrosis; perioperative period

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