Sclerotic effect of bleomycin on the submandibular gland: an experimental model

Int J Pediatr Otorhinolaryngol. 2013 Jun;77(6):943-6. doi: 10.1016/j.ijporl.2013.03.013. Epub 2013 Mar 30.


Objectives: To evaluate the sclerotic effect of bleomycin on the submandibular gland histopathologically and assess it as a possible alternative therapy for sialorrhea.

Methods: An experimental model was designed and 18 New Zealand white rabbits were used. The rabbits were divided into two groups: a bleomycin group (n=9) and a sham group (n=9). The submandibular glands of the bleomycin group were injected with 0.3 ml bleomycin (3mg/ml) while the sham group received 0.3 ml saline. Four weeks after the procedure, the glands were removed. Histopathological studies including hematoxylin-eosin and Masson's trichrome stain were carried out. The glands were evaluated for tissue inflammation, fibrosis, edema, lipomatosis, atrophy and congestion. To investigate apoptosis, terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-11-dUTP nick-end labeling (TUNEL) immunohistochemical staining was used.

Results: In the group injected with bleomycin, inflammation (n=8), edema (n=4), fibrosis (n=3), congestion (n=4) and lipomatosis (n=7) were observed. In the sham group, only lipomatosis was observed. The TUNEL assay results were 5.06 ± 1.18 (p<0.05) for acinar cells and 8.46 ± 0.82 (p<0.05) for ductal cells in the bleomycin group. This was significantly different from the results in the sham group.

Conclusions: Apoptosis, inflammation, fibrosis, edema, lipomatosis and congestion were observed in the ductal and acinar cells of the bleomycin group. Bleomycin may be an alternative treatment for sialorrhea cases. However, more research is needed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bleomycin / adverse effects*
  • Bleomycin / pharmacology
  • Disease Models, Animal
  • Female
  • Fibrosis / chemically induced
  • Fibrosis / pathology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Rabbits
  • Random Allocation
  • Reference Values
  • Sclerosis / chemically induced
  • Sclerosis / pathology
  • Sialorrhea / drug therapy*
  • Statistics, Nonparametric
  • Submandibular Gland / drug effects*
  • Submandibular Gland / pathology*


  • Bleomycin