Dose-Dependent Histopathological Alterations in the Small and Large Intestinal Mucosa of Syrian Golden Hamsters (Mesocricetus auratus) Following Cyclophosphamide Administration

Abstract

Background: Cyclophosphamide (CP) is a potent chemotherapeutic agent with well‑documented systemic toxicities. The gastrointestinal tract is particularly vulnerable, yet comparative effects on the small and large intestines remain underexplored. Aim: To evaluate dose‑dependent histopathological changes in the small and large intestines of female Syrian golden hamsters following CP administration. Methods: Twenty‑seven hamsters were divided into three groups: control (saline), therapeutic dose (100 mg/kg), and toxic dose (200 mg/kg). CP was administered intraperitoneally on days 1, 3, and 5. On day 7, intestinal tissues were harvested, fixed, and processed for histology. Sections were stained with Hematoxylin & Eosin (H&E) to assess epithelial and structural integrity, and Periodic Acid–Schiff (PAS) to evaluate goblet cell distribution and mucin content. Comparative analysis was performed between small intestinal villi and large intestinal crypts to determine site‑specific susceptibility. Results: At 100 mg/kg, the small intestine showed mild villous blunting and inflammatory infiltrates, whereas the large intestine remained largely intact. At 200 mg/kg, the small intestine exhibited severe villous fusion, epithelial denudation, and goblet cell depletion, while the large intestine demonstrated crypt distortion and marked mucin loss. Conclusion: CP induces dose‑dependent intestinal injury, with the small intestine displaying greater sensitivity than the large intestine. These findings highlight the importance of comparative gastrointestinal monitoring and the development of protective interventions during CP therapy.