title: Effects of tacrolimus and nifedipine, alone or in combination, on gingival tissues.
abstract: BACKGROUND
  The aim of this study is to compare gingival changes induced by short- and long-term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug-induced gingival overgrowth.
  
  
  METHODS
  Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8-week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24-week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry.
  
  
  RESULTS
  Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P <0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P <0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P <0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P <0.05).
  
  
  CONCLUSIONS
  Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug-induced gingival overgrowth.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, Istanbul Aydın University, Istanbul, Turkey.
authors.forename: Ferda
authors.initials: F
authors.lastname: Pamuk
authors.forename: Burcu Ozkan
authors.initials: BO
authors.lastname: Cetinkaya
authors.forename: Mustafa Yavuz
authors.initials: MY
authors.lastname: Gulbahar
authors.forename: Ayhan
authors.initials: A
authors.lastname: Gacar
authors.forename: Gonca Cayır
authors.initials: GC
authors.lastname: Keles
authors.forename: Zuleyha
authors.initials: Z
authors.lastname: Erisgin
authors.forename: Nurol
authors.initials: N
authors.lastname: Arik
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002452:Cell Count; D003094:Collagen / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D004338:Drug Combinations; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000187:drug effects / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D003094:Collagen; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; D009543:Nifedipine; D016559:Tacrolimus