Local amifostine administration mitigates chemotherapy-induced esophageal mucosal damage: A novel approach for targeted treatment in a rabbit model.

OBJECTIVE: Effective preventive measures for radiotherapy and chemotherapy-induced esophagitis are currently lacking. This study aims to investigate the local impact of chemotherapeutic agents on normal esophageal tissue and assess the cytoprotective effects of amifostine against chemotherapy-induced esophageal injury. METHODS: Twenty-four New Zealand white rabbits were randomly assigned to the control group, which only received saline; the cisplatin (DDP) group, which received 0.25 mg/ml of the chemotherapeutic drug (DDP); and the combined treatment group, which received pre-treatment with 0.8 mg/ml amifostine followed by 0.25 mg/ml DDP. Each group consisted of eight rabbits. A custom-made balloon device for targeted esophageal drug delivery was inserted into the esophagus, followed by the infusion of DDP and/or amifostine into the created space. After six days, rabbits were euthanized, and esophageal specimens were examined for mucosal damage. RESULTS: Macroscopically, compared with the control group, the DDP group exhibited significant thickening, edema, mucosal ulceration, and congestion in the infused esophageal region. Conversely, the combined treatment group showed mild thickening and a smooth or mildly congested mucosal surface. Microscopically, the DDP group displayed extensive mucosal detachment, edema, dilated submucosal blood vessels, and substantial infiltration of inflammatory cells. The combined treatment group exhibited partial mucosal detachment and moderate inflammatory cell infiltration in the submucosal and muscular layers, with few inflammatory cells in the muscle layer. CONCLUSION: This study provided evidence that damage caused by the local infusion of DDP might be reduced by pre-treatment of the cytoprotective agent amifostine.