Spermidine attenuates cisplatin-induced dorsal lingual injury through modulation of oxidative stress, inflammation, apoptosis, and epithelial proliferation in rats.

Cisplatin (CIS)-induced oral mucosal injury is a common complication of chemotherapy that is largely mediated by oxidative stress, inflammation, apoptosis, and impaired epithelial regeneration. Spermidine (SP), an endogenous polyamine, contributes to cellular homeostasis, tissue repair, and epithelial regeneration and has well-documented antioxidant, anti-inflammatory, and cytoprotective activities. The present investigation evaluated the protective impact of SP against CIS-induced dorsal tongue injury in adult albino rats. Four groups were created: control, SP, CIS, and SP-CIS. Tongue tissues were subjected to biochemical assessment of oxidative stress, inflammatory, and apoptotic markers, gene expression of Bcl-2 and Bax, histopathological examination, Ki-67 immunohistochemistry, morphometric analysis, and scanning electron microscopy. CIS administration induced marked oxidative stress, inflammation, and apoptosis, as evidenced by increased MDA, TNF-α, IL-6, caspase-3, and Bax expression, together with reduced SOD, total glutathione, and Bcl-2 expression. These alterations were associated with severe degeneration of the dorsal lingual mucosa, shortening and distortion of the lingual papillae, epithelial thinning, reduced Ki-67 immunoexpression, and marked surface morphological alterations. SP administration significantly attenuated these biochemical and molecular alterations, improved the architecture of the dorsal lingual papillae, enhanced epithelial proliferative activity, and markedly improved the histological findings. These results demonstrate that SP effectively attenuates CIS-induced dorsal lingual injury by attenuating oxidative stress, inflammation, and apoptosis while promoting epithelial regeneration, suggesting its potential protective agent for reducing CIS-associated oral toxicity. Further studies are needed to confirm the underlying mechanisms and translational relevance of these findings.