Narrow Results

Investigation of the radiation-induced bystander effect plays an important role in the understanding of the mechanisms of radiation response after low-dose irradiation. Sphingomyelinase (SMase) was activated by radiation and required the metal element for its activation. For further elucidation of the bystander effect, we investigated the relationship between its induction by acid SMase and a factor secreted from the irradiated tumor cells. In the cell culture medium transfer experiment after irradiation at a dose of 0.1 Gy, cell death was induced in non-irradiated cells. However, when cells received prior treatment with SMase inhibitor, cell death was not induced. When fluctuations in the activation of SMase and metal elements were detected, both intracellularly and extracellularly after irradiation, an increase in SMase activity and Zn concentration occurred within the cells at 5 min and outside of the cells at 15 min after irradiation. This increase in zinc concentration at 15 min after irradiation was suppressed by treatment with SMase inhibitor. These results suggest that activation of SMase, which is related to the bystander effect, is dependent on zinc.

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.