Oral mucosa alterations induced by cyclosporin in mice: morphological features.
OBJECTIVE
The mechanisms involved in the pathogenesis of cyclosporin A-induced gingival hyperplasia are not well understood. The present work aimed at developing a mouse model with the characteristics of the human process, i.e. time of appearance, dose dependency and the capacity of developing in a variety of genetic backgrounds. This model would present the advantages of using a very well known animal species, small and easy to handle, with a number of experimental reagents (antibodies, etc.) already available against its products.


METHODS
Three different strains of mice were used: CBA, F1(C57Bl x DBA), Balb/c. Groups of mice received different concentrations of cyclosporin A (CSA) (10 mg/kg, 25 mg/kg and 40 mg/kg body weight) intraperitoneally five times a week. Anatomical and histological alterations were recorded at various time intervals.


RESULTS
All strains of mice presented gingival hyperplasia after 8 weeks of CSA treatment. A dose-dependency was observed with regard to the time of first appearance of alterations. Increased redness was seen in all animals at the sixth week, independent of the dosage used. Histologic examination exhibited increased vascularization, epithelial and connective tissue thickening, edema and a mononuclear infiltrate.


CONCLUSIONS
It was possible to develop CSA-induced gingival hyperplasia in mice with the characteristics described in humans and other species. The use of this animal model may help in the elucidation of the process involved in CSA-induced gingival overgrowth.
Meller
A T
AT
Department of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Rumjanek
V M
VM
Sansone
C
C
Allodi
S
S
D000818:Animals; D003238:Connective Tissue / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004487:Edema / Q000139:chemically induced; D004848:Epithelium / Q000187:drug effects; D005260:Female; D005881:Gingiva / Q000098:blood supply / Q000187:drug effects; D005885:Gingival Hyperplasia / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009061:Mouth Mucosa / Q000098:blood supply / Q000187:drug effects*; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine