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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/F128    most recent 00577.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, H. T. Articles by Kim, M. Search for Related Content PubMed PubMed Citation Articles by Lee, H. T. Articles by Kim, M.

Sevoflurane protects against renal ischemia and reperfusion injury in mice via the transforming growth factor-β₁ pathway

¹Department of Anesthesiology and ⁴Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York; ²Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona; and ³Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 3 December 2007 ; accepted in final form 18 April 2008

We previously demonstrated that several clinically utilized volatile anesthetics including sevoflurane protected against renal ischemia-reperfusion (IR) injury by reducing necrosis and inflammation in vivo. We also demonstrated that volatile anesthetics produced direct anti-necrotic and anti-inflammatory effects in cultured renal tubules via mechanisms involving the externalization of phosphatidylserine and subsequent release of transforming growth factor (TGF)-β₁. In this study, we tested the hypothesis that volatile anesthetic-mediated renal protection requires TGF-β₁ and SMAD3 signaling in vivo. We subjected TGF-β₁+/+, TGF-β₁+/–, SMAD3+/+, or SMAD3–/– mice to renal IR under anesthesia with pentobarbital sodium or with sevoflurane. Although TGF-β₁+/+ and SMAD3+/+ mice were significantly protected against renal IR injury under sevoflurane anesthesia with reduced necrosis and inflammation, TGF-β₁+/– mice and SMAD3–/– mice were not protected against renal IR with sevoflurane. Furthermore, a neutralizing TGF-β₁ antibody blocked renal protection with sevoflurane in TGF-β₁+/+ mice. Sevoflurane caused nuclear translocation of SMAD3 and reduced the TNF--induced nuclear translocation of NF-B in primary cultures of proximal tubules from TGF-β₁+/+ but not in TGF-β₁+/– mice. Finally, sevoflurane protected against necrosis induced with hydrogen peroxide in primary cultures of proximal tubules from TGF-β₁+/+ mice or SMAD3+/+ mice but not in proximal tubules from TGF-β₁+/– or SMAD3–/– mice. Therefore, we demonstrate in this study that sevoflurane-mediated renal protection in vivo requires the TGF-β₁SMAD3 signaling pathway.

acute renal failure; inflammation; necrosis; SMAD3