Effects of oral ısotretinoin on normal and wounded nasal mucosa: an experimental study

Eur Arch Otorhinolaryngol. 2018 Dec;275(12):3025-3031. doi: 10.1007/s00405-018-5190-2. Epub 2018 Oct 31.

Abstract

Background: We aimed to investigate the effect of systemic isotretinoin therapy on normal and wounded nasal septal mucosa histopathologically in an experimental rabbit model.

Methods: Circular mucosal defect with a 7 mm diameter was made in the left septum of 12 New Zealand white rabbits. The rabbits were divided into two groups (six rabbits in each group) oral isotretinoin was given with olive oil at the operation day to the first group. The control group was only oil given group. The harvested septum mucosas were divided into four groups (1-wounded-drug given side, 2-unwounded and drug-given side, 3-wounded-control and 4-unwounded-control side). The diameter of the defect, mucosal thickness, epithelial thickness, ciliated cell level, goblet cell level and inflammation were evaluated every week for 4 weeks.

Results: At both wounded and normal side, thinning of normal respiratory ciliated epithelium was observed in the postoperative period. In study group at the wounded side; mean mucosal thickness was measured 139.66 µ (± 26.24), and in the control group, mean mucosal thickness was 238.33 µ (± 39.7) at the wounded side. (p < 0.001). The difference between the groups in thickness of normal septal mucosa was also statistically significant (p = 0.016) [190 µ (± 14.6) and 256.66 µ (± 44.66)]. The average cilia level was observed 1.16 in the wounded study group, while the average level was 2.33 in the wounded control group (p = 0.012). Average score measurements of the regenerated mucosa suggested that isotretinoin-given wounded animals have reduced goblet cell recovery, compared to the control both on the regenerated and unwounded mucosas (p = 0.007, p = 0.002, respectively). Inflammation was significantly higher in the wounded isotretinoin group (p = 0.018).

Conclusion: Oral isotretinoin has negative effects on epithelial and ciliary regeneration, significantly reduces mucosal thickness and goblet cell counts of the normal and regenerated mucosa, causes severe inflammation and significant reactive changes.

Keywords: Healing; Nasal mucosa; Oral isotretinoin.

MeSH terms

  • Animals
  • Cell Count
  • Cilia / drug effects
  • Cilia / pathology
  • Cilia / physiology
  • Dermatologic Agents / pharmacology*
  • Goblet Cells / drug effects
  • Goblet Cells / physiology
  • Inflammation / pathology
  • Isotretinoin / pharmacology*
  • Male
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / injuries*
  • Nasal Mucosa / pathology
  • Nasal Mucosa / physiopathology
  • Nasal Septum / surgery
  • Rabbits
  • Regeneration / drug effects

Substances

  • Dermatologic Agents
  • Isotretinoin