Iron overload causes excessive iron deposition in extrahepatic organs, including the tongue. This study aims to compare the deferiprone and/or resveratrol treatments for the alleviation of iron overload-induced tongue injury in rats. Rats were divided into 6 groups: control group, iron-overloaded group, recovery group where rats were left to recover from iron overload, deferiprone-treated group, resveratrol-treated group, and combined deferiprone/resveratrol-treated group. Iron was administered for 4 weeks, while all treatment options were given for the subsequent 4 weeks. After 8 weeks, all rats were sacrificed; the serum iron profile was estimated, and the tongues were assessed by histopathological, tumour necrosis factor alpha (TNF-α) immunohistochemical, histomorphometric, and ultrastructural evaluations. Serum iron parameters were significantly increased in iron-overloaded rats and decreased to control levels only in the combined group. The iron-overloaded tongues demonstrated lost lingual papillae, coarse keratohyalin granules, vacuolated epithelial cells, degenerated muscle fibers, and congested blood vessels. Compared to the control rats, this group revealed a significant decrease in the epithelial layer thickness (550.7 vs. 763.4µm), papillae height (441.4 vs. 849.7µm), and myofiber diameter (58.5 vs. 98.6µm), and increased lamina propria thickness (305.1 vs. 176.8µm), fibrosis index (33.4 vs. 8.6%), and TNF-α immunoexpression (1.16 vs. 0.63 optical density). Additionally, the ultrastructure showed hyperkeratinized papillae, wide interpapillary spaces, flat fungiform papillae, and lost gustatory pores. All these parameters were improved in the recovery, deferiprone, and resveratrol groups to different degrees, while the combined deferiprone/resveratrol treatment was the best option.
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