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). CONCLUSION: 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.
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). CONCLUSION: 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.
Authors: Mehmet Kanbay; Emine M Onal; Baris Afsar; Tuncay Dagel; Aslihan Yerlikaya; Adrian Covic; Nosratola D Vaziri Journal: Int Urol Nephrol Date: 2018-05-04 Impact factor: 2.370
Authors: A E Gordeeva; A A Temnov; A A Charnagalov; M G Sharapov; E E Fesenko; V I Novoselov Journal: Dig Dis Sci Date: 2015-08-02 Impact factor: 3.199
Authors: Emad S Osman; Hanan F Khafagy; Yasser M Samhan; Mona M Hassan; Faten M El-Shanawany; Abdel Rahman M Fathallah; Gehan G El-Fandy Journal: Korean J Anesthesiol Date: 2012-07-24