Effects of cyclosporin, phenytoin, and nifedipine on the synthesis and degradation of gingival collagen in tufted capuchin monkeys (Cebus apella): histochemical and MMP-1 and -2 and collagen I gene expression analyses.
BACKGROUND
The purpose of this experimental study was to evaluate the collagen fiber distribution histologically after phenytoin, cyclosporin, or nifedipine therapy and to correlate it with collagen I and matrix metalloproteinase (MMP)-1 and -2 gene expression levels.


METHODS
Gingival samples from the canine area were obtained from 12 male monkeys (Cebus apella). The mesial part of each sample was assessed by reverse transcription-polymerase chain reaction, whereas the distal part was processed histologically for picrosirius red and hematoxylin and eosin stainings, as well as for collagen IV immunostaining. One week after the first biopsy, the animals were assigned to three groups that received daily oral dosages of cyclosporin, phenytoin, or nifedipine for 120 days. Additional gingival samples were obtained on days 52 and 120 of treatment from two animals from each group on the opposite sides from the first biopsies.


RESULTS
Picrosirius red staining showed a predominance of mature collagen fibers in the control group. Conversely, there was an enlargement of areas occupied by immature collagen fibers in all groups at days 52 and 120, which was not uniform over each section. There was a general trend to lower levels of MMP-1 gene expression on day 52 and increased levels on day 120. Phenytoin led to increased levels of MMP-2 and collagen I gene expression on day 120, whereas the opposite was observed in the nifedipine group.


CONCLUSIONS
Cyclosporin, phenytoin, and nifedipine led to phased and drug-related gene expression patterns, resulting in impaired collagen metabolism, despite the lack of prominent clinical signs.
Kanno
Cláudia M
CM
Post-Graduation Program, Dental School of Araçatuba, São Paulo State University, Araçatuba, SP, Brazil. cmkanno@foa.unesp.br
Oliveira
José A
JA
Garcia
José F
JF
Castro
Alvimar L
AL
Crivelini
Marcelo M
MM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001391:Azo Compounds; D001706:Biopsy; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002428:Cebus; D003094:Collagen / Q000032:analysis / Q000187:drug effects*; D024042:Collagen Type I / Q000032:analysis / Q000187:drug effects; D024141:Collagen Type IV / Q000032:analysis / Q000187:drug effects; D004396:Coloring Agents; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D005891:Gingivitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000235:genetics; D009543:Nifedipine / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000927:Anticonvulsants; D001391:Azo Compounds; D002121:Calcium Channel Blockers; D024042:Collagen Type I; D024141:Collagen Type IV; D004396:Coloring Agents; D004791:Enzyme Inhibitors; C009798:C.I. direct red 80; D010672:Phenytoin; D016572:Cyclosporine; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D009543:Nifedipine