Propofol pretreatment reduces ceramide production and attenuates intestinal mucosal apoptosis induced by intestinal ischemia/reperfusion in rats.
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 anesthetic with antioxidant properties, could reduce ceramide production, and consequently, 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 malondialdehyde and the activities of superoxide dismutase were assessed by colorimetric analyses. Ceramide generation and sphingomyelinase mRNA expression in intestinal 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).


CONCLUSIONS
The findings indicate that propofol pretreatment attenuates II/R-induced intestinal epithelial apoptosis, which might be attributable to its antioxidant property modulating the ceramide pathway.
Liu
Ke-Xuan
KX
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No.58, Zhongshan 2th Rd., Guangzhou, China, 510080. liukexuan807@yahoo.com.cn
Chen
Shu-Qing
SQ
Huang
Wen-Qi
WQ
Li
Yun-Sheng
YS
Irwin
Michael G
MG
Xia
Zhengyuan
Z
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002518:Ceramides / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D046529:Microscopy, Electron, Transmission; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism
D018686:Anesthetics, Intravenous; D002518:Ceramides; D012333:RNA, Messenger; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D013108:Sphingomyelin Phosphodiesterase; D015742:Propofol