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Background <p>Bisphosphonates (BPs) are widely used antiresorptive agents for skeletal disorders; however, their adverse effects on oral soft tissues, particularly the lingual mucosa and gustatory apparatus, remain incompletely understood. Nano-chitosan has emerged as a promising biomaterial with cytoprotective and regenerative properties in orofacial tissues, indicating potential utility in mitigating BP-associated mucosal injury.</p> Objectives <p>To evaluate the protective effects of topical nano-chitosan on alendronate-induced lingual injury in a rat model.</p> Methods <p>Thirty adult male Wistar rats were randomized into three groups (<i>n</i> = 10 each): control (Group I), alendronate-treated (1&#xa0;mg/kg, subcutaneously, three times weekly for 4 weeks), and alendronate plus daily topical nano-chitosan (0.5 mL/day). Lingual tissues were examined using histology (H&amp;E and Masson’s trichrome), immunohistochemistry (PCNA), histomorphometry, scanning electron microscopy, and RT-qPCR for α-gustducin (GNAT3).</p> Results <p>Alendronate induced significant lingual alterations, including reduced papillary height (48%), decreased epithelial proliferation (80% PCNA expression), increased disorganized collagen deposition (approximately 2.5-fold), ultrastructural disruption, and downregulation of GNAT3 (all <i>p</i> &lt; 0.001 vs. control). Nano-chitosan treatment attenuated these changes, restoring papillary morphometry, PCNA expression (27.66% vs. 29.60%, <i>p</i> = 0.127), and collagen content (9.45% vs. 8.49%, <i>p</i> = 0.538) to levels comparable with controls. GNAT3 expression was partially restored but remained significantly reduced compared with controls.</p> Conclusion <p>Topical nano-chitosan mitigates alendronate-induced lingual injury in rats by improving epithelial architecture and proliferation and partially restoring GNAT3 transcript levels. No functional gustatory assessment was performed; therefore, conclusions regarding taste function recovery are not drawn from the present data. These findings indicate a modulatory rather than fully restorative effect on BP-associated oral mucosal alterations and support further preclinical and translational investigation.</p> Graphical Abstract <p></p>

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Topical nano-chitosan mitigates alendronate-induced lingual mucosal injury in rats: histological, immunohistochemical, molecular, and ultrastructural study

  • 期刊论文

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  • 发表日期：

    2026年7月22日

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  • Abeer Ezat Wahba,
  • Fatema F. Elturki,
  • Ghada A. Gehani,
  • Hamza Alasbily,
  • Muna S. Elburki,
  • Adel M. Alqarni,
  • Fahad A. Alshahrani,
  • Mubarak Alaklobie,
  • Mohammed M. Alruwaili,
  • Saleh A. Alghamdi,
  • Helal G. Alanazi

摘要

Background

Bisphosphonates (BPs) are widely used antiresorptive agents for skeletal disorders; however, their adverse effects on oral soft tissues, particularly the lingual mucosa and gustatory apparatus, remain incompletely understood. Nano-chitosan has emerged as a promising biomaterial with cytoprotective and regenerative properties in orofacial tissues, indicating potential utility in mitigating BP-associated mucosal injury.

Objectives

To evaluate the protective effects of topical nano-chitosan on alendronate-induced lingual injury in a rat model.

Methods

Thirty adult male Wistar rats were randomized into three groups (n = 10 each): control (Group I), alendronate-treated (1 mg/kg, subcutaneously, three times weekly for 4 weeks), and alendronate plus daily topical nano-chitosan (0.5 mL/day). Lingual tissues were examined using histology (H&E and Masson’s trichrome), immunohistochemistry (PCNA), histomorphometry, scanning electron microscopy, and RT-qPCR for α-gustducin (GNAT3).

Results

Alendronate induced significant lingual alterations, including reduced papillary height (48%), decreased epithelial proliferation (80% PCNA expression), increased disorganized collagen deposition (approximately 2.5-fold), ultrastructural disruption, and downregulation of GNAT3 (all p < 0.001 vs. control). Nano-chitosan treatment attenuated these changes, restoring papillary morphometry, PCNA expression (27.66% vs. 29.60%, p = 0.127), and collagen content (9.45% vs. 8.49%, p = 0.538) to levels comparable with controls. GNAT3 expression was partially restored but remained significantly reduced compared with controls.

Conclusion

Topical nano-chitosan mitigates alendronate-induced lingual injury in rats by improving epithelial architecture and proliferation and partially restoring GNAT3 transcript levels. No functional gustatory assessment was performed; therefore, conclusions regarding taste function recovery are not drawn from the present data. These findings indicate a modulatory rather than fully restorative effect on BP-associated oral mucosal alterations and support further preclinical and translational investigation.

Graphical Abstract