title: The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats--a morphological evaluation.
abstract: BACKGROUND
  Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats.
  
  
  METHODS
  Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar.
  
  
  RESULTS
  After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P>0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the Vf and Vcf (P<0.05).
  
  
  CONCLUSIONS
  Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related.
authors.affiliation: Department of Periodontology Araraquara Dental School, University of State of São Paulo, Araraquara, São Paulo, Brazil. canassar@yahoo.com
authors.forename: C A
authors.initials: CA
authors.lastname: Nassar
authors.forename: P O
authors.initials: PO
authors.lastname: Nassar
authors.forename: D C
authors.initials: DC
authors.lastname: Andia
authors.forename: M R
authors.initials: MR
authors.lastname: Guimarães
authors.forename: L C
authors.initials: LC
authors.lastname: Spolidorio
mesh_terms: D000818:Animals; D002452:Cell Count; D003094:Collagen / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology; D005885:Gingival Hyperplasia / Q000139:chemically induced / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D003094:Collagen; D016559:Tacrolimus