The effect of ginkgo biloba extract (EGb 761) pretreatment on intestinal epithelial apoptosis induced by intestinal ischemia/reperfusion in rats: role of ceramide.
Apoptosis was demonstrated to be a major mode of intestinal epithelial cell death caused by intestinal ischemia/reperfusion (II/R). Ceramide has been proposed as a messenger for apoptosis. The present study was aimed to investigate the effect of Ginkgo biloba extract 761 (EGb 761) pretreatment on II/R-induced intestinal mucosal epithelial apoptosis in rats and the mechanism related to ceramide. The rat model of II/R injury was produced by clamping superior mesenteric artery for 60 min followed by reperfusion for 180 min. Twenty four rats were randomly allocated into Sham, II/R and EGb + II/R groups. In EGb + II/R group, EGb 761 (100 mg/kg per day) was administered intragastrically for 7 days before the surgery. Animals in II/R and sham groups were treated with equal volume of normal saline solution. Intestinal mucosal epithelial apoptosis was detected via electron microscopy and TUNEL method. Lipid peroxidation in intestinal mucosa was determined by detecting the malondialdehyde level and the activities of superoxide dismutase and peroxidase glutathione. The ceramide generation and sphingomyelinase (SMase) mRNA expression in intestinal mucosa were determined by high performance, thin layer chromatography, and RT-PCR, respectively. II/R caused intestinal mucosal epithelial apoptosis and over-production of the ceramide accompanied by up-regulation of SMase mRNA expression and increases of lipid peroxidation. EGb 761 pretreatment significantly decreased apoptosis index, and concurrently reduced the ceramide generation accompanied by down-regulation of SMase expression and inhibition of lipid peroxidation. The findings indicate that EGb 761 pretreatment attenuates II/R-induced intestinal epithelial apoptosis, which might be attributable to its antioxidant action of mediating ceramide pathway.
Liu
Ke-Xuan
KX
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. liukexuan807@yahoo.com.cn
He
Wei
W
Rinne
Timo
T
Liu
Ying
Y
Zhao
Ming-Qi
MQ
Wu
Wei-Kang
WK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002518:Ceramides / Q000378:metabolism*; D004195:Disease Models, Animal; D020441:Ginkgo biloba / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
D002518:Ceramides; D010936:Plant Extracts; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase