Establishment of Irinotecan-Induced Oral Mucositis Hamster Model and Evaluation of Therapeutic Agents

Chemotherapy-induced oral mucositis is a frequent and debilitating adverse effect that impairs nutritional status and interrupts cancer therapy. Although 5-fluorouracil-induced animal models of oral mucositis are well established, irinotecan, widely used for colorectal, lung, and pancreatic cancers, has also been associated with oral mucosal injury; however, no standardized preclinical model exists. This study aimed to establish a reproducible hamster model of irinotecan-induced oral mucositis and evaluate the prophylactic and therapeutic efficacy of topical hangeshashinto (HST) compared with dexamethasone. Male Syrian hamsters received intraperitoneal irinotecan (100, 150, or 200 mg/kg) on Day 0, followed by localized mucosal injury induced by 50% acetic acid. Ulcer area, body weight, histopathology, peripheral blood count, and myeloperoxidase (MPO) activity were evaluated. HST (10% aqueous solution) or dexamethasone (0.01% elixir) was administered topically once daily either prophylactically (Days -3 to 0) or therapeutically (from Day 0 onward). Ulcer area increased in a dose-dependent manner, peaking on Day 4. The 200 mg/kg dose yielded consistent lesion formation with transient weight loss. Histopathological examination revealed dense neutrophilic infiltration and epithelial disruption. MPO activity was significantly elevated on Days 4 and 7. Prophylactic HST significantly reduced the peak and cumulative ulcer areas, whereas dexamethasone delayed healing. The 200 mg/kg irinotecan plus acetic acid hamster model thus provides a reliable platform for investigating oral mucositis. HST, particularly when administered prophylactically, exhibited better efficacy than dexamethasone, potentially through modulation of inflammatory responses and attenuation of oxidative stress. This model may facilitate further mechanistic studies and the development of preventive strategies for chemotherapy-induced oral mucositis.