title: Histopathological and morphological alterations of periodontium in rats treated with tacrolimus and cyclosporine.
abstract: OBJECTIVE
  To evaluate and compare the possible morphological and histopathological changes in gingival tissue of rats under the administration of cyclosporine and tacrolimus. The present study was motivated by the high prevalence of gingival overgrowth observed in subjects under cyclosporine regimens and by studies reporting a significant decrease in gingival overgrowth after the substitution of tacrolimus.
  
  
  METHODS
  Five Sprague-Dawley rat groups were administered therapeutic and greater-than-therapeutic doses of cyclosporine and tacrolimus over 54 days. The control group of 10 animals received distilled water as a placebo. The cyclosporine group was divided into two subgroups of 10 animals each, one receiving 10 mg/kg/day (CsA1) and one receiving 30 mg/kg/day (CsA2). The tacrolimus group was also divided in two subgroups of 10 animals each, receiving 3.2 mg/kg/day (Tcr1) or 6.4 mg/kg/day (Tcr2).
  
  
  RESULTS
  Gingival overgrowth was higher in the group that was administered the higher cyclosporine dosage (CsA2) than in the group that received the therapeutic dosage, showing a positive relation between dosage and severity of gingival overgrowth. Hypercellularity, vascular congestion and focal inflammatory exudation were observed in the CsA2 subgroup only. There were no morphological or histological alterations in gingival tissue in either tacrolimus subgroups.
  
  
  CONCLUSIONS
  Cyclosporine can induce adverse morphological and histopathological changes in gingival tissue of rats, and these effects are dose-dependent. Tacrolimus induced no gingival alterations in this rat model.
authors.affiliation: Department of Periodontology, School of Dentistry, Federal University of Minas Gerais, Brazil. focperio@uol.com.br
authors.forename: Eugênio José Pereira
authors.initials: EJ
authors.lastname: Lages
authors.forename: Luís Otávio Miranda
authors.initials: LO
authors.lastname: Cota
authors.forename: Elizabeth Maria Bastos
authors.initials: EM
authors.lastname: Lages
authors.forename: José Eustáquio
authors.initials: JE
authors.lastname: Costa
authors.forename: Fernando Oliveira
authors.initials: FO
authors.lastname: Costa
authors.forename: Fernando Iiveira
authors.initials: FI
authors.lastname: Costa
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D010519:Periodontium / Q000187:drug effects* / Q000473:pathology; D010919:Placebos; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D010919:Placebos; D016572:Cyclosporine; D016559:Tacrolimus