The Protective Effect Of Local Amifostine On Esophageal Injury Induced By DDP

Objective: To investigate the protective effect of amifostine(cell protective agent)on esophageal injury induced by chemotherapeutic drug(DDP)through specially designed drug delivery system and observe look for a new method for clinical using of amifostine in order to reduce its toxocity.Aiming at providing theoretical basis on local targeted therapy for esophageal carcinoma.Methods:1 The experimental study of the local drug delivery: We designed a special drug delivery system that can block up the esophagus lumen with two sacculuses,forming a space between the two sacculuses,and then perfusing the DDP(or/and)amifostine liquid to the esophageal space.2 The esophageal injury induced by local DDP in rabbit:36 New Zealand white rabbits were divided into three groups: control group(control),0.25mg/mL cisplatin(DDP)group and 0.5mg/mL DDP group.The esophagus spaces were perfused with saline in control and 0.25mg/mL DDP and 0.5mg/mL DDP in another two groups for 40 min.The rabbits were sacrified at 6 and 14 days after perfusions respectively and specimens were fixed with formalin for pathological examination.3 The esophageal injury induced by DDP:24 rabbits were randomly divided into four groups:control group(control),cisplatin group alone(DDP),amifostine group(AMI)alone and combined therapy group(DDP+AMI).The esophagus space was perfused with saline for 40 min in control.In the DDP or AMI group,the esophagus space was perfused with saline for 20 min,Then saline was removed and 0.5mg/mL DDP(or 0.2mg/mL amifostine)was injected for 40 min again.In DDP+AMI group: The esophagus space was perfused with 0.2mg/mL amifostine liquid for 20 min before DDP.The rabbits were sacrified and specimens were fixed with formalin for pathological examination AT 6 day after perfusion.Results:1 The esophageal injury induced by local DDP in rabbit: The epithelium of esophagus was normal in contral group at different time after perfusion.In the 0.5mg/mL DDP group,the esophageal epithelium was in part or full-thickness shedding.The mucosa was edematous and submucosal blood vessels was congestive.There is a large number of inflammatory cells in submucosa had infiltrated,There is obvious difference in esophageal injury degree and number of inflammatory cells between in 0.5mg/mL DDP group and 0.25mg/mL DDP or control group(p<0.01).2 The protective effect of local amifostine on esophageal injury induced by DDP: Gross appearance: The esophagus of the DDP group significantly expanded and was edematous on perfusion site.The mucosal surface was covered with off-white "pseudomembranous".The mucosa had obvious hyperemia and erosions.The esophagus of the combined therapy group mildly expanded The mucosal surface was smooth and had no "pseudomembranous".Light microscope: The esophageal epithelium of the DDP group was in part or full-thickness shedding.The mucosa was edematous and submucosal blood vessels was congestive.There was a large number of inflammatory cells in submucosal and some also invaded the muscularis.The esophageal epithelium of the combined therapy group was in part shedding.There were a large number of inflammatory cells in mucosa and some in submucosa and muscularis.There is obvious difference in esophageal injury degree and number of inflammatory cells between in DDP+AMI and DDP group(P>0.01).Conclusion:1 shif-made davice of local using drug for the esophageal carcinoma may be feasible.It can increase the local drug concentration and reduce the systemic side effects of amifostine.2 The reversible esophageal injury can be induced by greater than 0.5mg/mL DDP in rabbit.It is necessary that the concentration of local DDP control between 0.25 and 0.5mg/mL.3 Threr is a protective effect of amifostine on esophageal injury induced by chemotherapeutic drug through specially designed drug delivery system.It can provide a new method for the clinical application of amifostine.