Propofol Pretreatment Reduces Ceramide Production and Attenuates Intestinal Mucosal Apoptosis Induced by Intestinal Ischemia/Reperfusion in Rats Ke-Xuan Liu, PhD, MD* Shu-Qing Chen, PhD, MD† Wen-Qi Huang, MD* Yun-Sheng Li, MD* Michael G. Irwin, MD‡ Zhengyuan Xia, PhD, MD‡ BACKGROUND: Apoptosis has been shown to be a major mode of intestinal epithelial cell death caused by intestinal ischemia/reperfusion (II/R), a condition that is associated with increased oxidative stress. Ceramide has been proposed as a messenger of apoptosis. We investigated if pretreatment with propofol, an anes- thetic with antioxidant properties, could reduce ceramide production, and conse- quently, mucosal epithelial apoptosis induced by II/R in rats. METHODS: Rat II/R injury was produced by clamping the superior mesenteric artery for 1 h followed by 3 h of reperfusion. Thirty rats were randomly allocated into control, injury (II/R) and propofol (pretreatment) groups (n = 10 per group). In the propofol group, propofol 50 mg/kg, a dose that has been shown to cause the loss of reflex responses to a painful stimulus while remaining sensitive to skin incision in rats, was administered intraperitoneally 30 min before inducing intestinal ischemia, while animals in control and untreated injury groups received an equal volume of intralipid. Intestinal mucosal epithelial apoptosis was detected via electron microscopy and TUNEL analysis. Lipid oxidation product malondialde- hyde and the activities of superoxide dismutase were assessed by colorimetric analyses. Ceramide generation and sphingomyelinase mRNA expression in intes- tinal mucosa were determined by high performance thin layer chromatography and reverse transcriptase polymerase chain reaction, respectively. RESULTS: II/R caused intestinal mucosal epithelial apoptosis and over-production of ceramide accompanied by up-regulation of sphingomyelinase mRNA expression and increases in lipid oxidation (all P  0.01 versus control). Propofol pretreatment significantly attenuated these changes (all P  0.01, propofol versus injury). CONCLUSION: The findings indicate that propofol pretreatment attenuates II/R- induced intestinal epithelial apoptosis, which might be attributable to its antioxi- dant property modulating the ceramide pathway. (Anesth Analg 2008;107:1884 –91) Intestinal ischemia/reperfusion (II/R) injury is a potentially serious consequence of acute mesenteric ischemia, hemorrhagic, traumatic or septic shock, se- vere burns or some surgical procedures, including small bowel transplantation and abdominal aortic sur- gery. 1 II/R leads not only to injury of the intestine itself, but also involves severe destruction of distant tissue due to disruption of the intestinal mucosal barrier which causes a systemic inflammatory reaction. II/R can even result in multiple organ dysfunction. 2,3 Intestinal mucosal epithelial cells are the main component of the intestinal mucosal barrier. Apopto- sis is a major mode of cell death in the destruction of rat small intestinal epithelial cells induced by ischemia and I/R injury. 4–6 Therefore, prophylactic antiapop- totic treatment could be an effective therapeutic strat- egy for the prevention of II/R injury, which has been demonstrated by various studies. 7–9 Ceramide, a novel second messenger, plays an important role in a variety of physiologic and patho- logic events, including apoptosis and injuries. 10 Modulation of ceramide levels may be regarded as a novel therapeutic approach. 11 The intracellular con- centration of ceramide can be influenced by many inducers, including reactive oxygen species (ROS) and IR injury. 12 Recently, we demonstrated that ceramide contributes to the intestinal mucosal cell apoptosis induced by II/R. 9 Propofol, an IV anesthetic with antioxidant proper- ties, 13,14 is commonly used for the induction and From the Departments of *Anesthesiology, †Gynecology and Obstetrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; and ‡Department of Anesthesiology, University of Hong Kong, Hong Kong SAR, China. Accepted for publication May 7, 2008. Supported, in part, by a grant from National Natural Science Foundation of China (No: 30672021, to K.X.L.). The authors K.X.L. and Z.X. share senior authorship. Address correspondence and reprint requests to Dr. Ke-Xuan Liu, Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No.58, Zhongshan 2th Rd., Guangzhou, China, 510080. Address e-mail to liukexuan807@yahoo.com.cn. Copyright © 2008 International Anesthesia Research Society DOI: 10.1213/ane.0b013e3181884bbf Vol. 107, No. 6, December 2008 1884