The Effects of Hesperidin on the Healing Process of Cleft Lip Surgical Wounds in Rats: A Histological Evaluation and Therapeutic Analysis

Document Type : Original

Authors

1 Department of Orthodontics, Faculty of Dentistry, Dental Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

2 Professor of Oral and Maxillofacial Pathology, Faculty of Dentistry, Dental Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

3 Dentist, Mazandaran University of Medical Sciences, Sari, Iran.

4 Professor of Pharmaceutics, Mazandaran University of Medical Sciences, Sari, Iran.

5 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

6 Periodontist, Researcher, Mazandaran, Sari, Iran.

7 PhD in Clinical Biochemistry, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

10.22038/ijorl.2025.85555.3890

Abstract

Introduction:
Cleft lip and palate are the most common congenital craniofacial anomalies, and inadequate treatment of these defects may lead to serious psychosocial and economic consequences. Hesperidin, a flavanone extracted from citrus fruit peels, is a potent antioxidant. However, no study has yet investigated the effects of hesperidin on surgical wound healing in cleft lips. The aim of the present study was to evaluate the histological effects of hesperidin on the healing process of surgically induced cleft lip wounds in rats.
Materials and Methods:
In this in vivo study, sixteen male Wistar rats were randomly divided into four groups: the control group (normal saline), intervention group 1 (25 mg/kg hesperidin), intervention group 2 (50 mg/kg hesperidin), and intervention group 3 (100 mg/kg hesperidin). A surgical wound was created on the left upper lip of each rat and sutured in two layers. The treatments were administered for 21 days. On day 28 post-surgery, the rats were euthanized, and histopathological analyses were performed to evaluate epithelial proliferation, inflammatory cell density, neovascularization, fibroblast proliferation, and collagen deposition. The samples were stained with hematoxylin and eosin and Masson’s trichrome stains. Statistical significance was set at P< 0.05.
Results:
The findings showed that the mean scores for fibroblast proliferation, collagen deposition, and inflammatory cell density were significantly higher in the placebo group compared to the 100 mg/kg hesperidin group (P= 0.006, P =0.009, and P = 0.035, respectively). Conversely, epithelial proliferation was significantly higher in the 100 mg/kg hesperidin group compared to the placebo group (P= 0.006). However, higher doses of hesperidin resulted in reduced collagen deposition and fibroblast proliferation, although these differences were not statistically significant (P> 0.05).
 
Conclusion:
Administration of 100 mg/kg hesperidin decreased fibroblast proliferation, collagen deposition, and inflammatory cell density, while increasing epithelial proliferation during the healing of surgically induced cleft lip wounds in rats. These results suggest that hesperidin may modulate wound repair and contribute to reduced scar formation, which could be particularly beneficial in the aesthetic zone.
Keywords: Cleft Lip, Hesperidin, Histopathological Techniques, Rats, Wound Healing

Keywords

Main Subjects

References

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Iranian Journal of Otorhinolaryngology
Volume 37, Issue 6
November and December 2025
Pages 291-302

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