Does nifedipine aggravate cyclosporin--induced gingival overgrowth? An experiment in rats.
BACKGROUND
Nifedipine (NIF) may aggravate cyclosporin A (CsA)-induced gingival overgrowth because the potentiated gingival overgrowth has been observed in the patients treated with CsA and NIF. The purpose of this study was to evaluate whether NIF could aggravate the CsA-induced gingival overgrowth in a rat model.


METHODS
Ninety male Sprague-Dawley rats were divided into 6 groups: the first group received 8 mg/kg of CsA daily by gastric feeding for 6 weeks; the second and third groups received NIF daily at a dosage of 10 or 50 mg/kg; the fourth and fifth groups received CsA (8 mg/kg) and NIF (10 or 50 mg/kg); and the sixth group received solvents as a negative control. Gingival dimensions (including bucco-lingual depth, mesio-distal width, and vertical height) were assessed bi-weekly from impressed stone models of the mandibular incisal region. At the end of the experiment, the animals were sacrificed. Following histopathological procedures, serial horizontal sections were obtained at the base of the central incisal papilla. Two tissue levels were selected for histometric analysis. Level 1 was defined as the point where the lingual gingiva embraced the bucco-lingual midpoint of the roots and the level 2 as the point where the lingual gingiva at the enamel-dentinal junction approximated the bucco-proximal angle of the roots. The bucco-lingual depth and the mesio-distal width of the papilla were recorded on 5 consecutive sections at the 2 levels, respectively.


RESULTS
At the 6-week observations, the gingival dimensions (including the depth, width, and height) significantly increased after CsA therapy and the increasing treatment duration; however, only the mesio-distal width increased after NIF therapy. For NIF therapy alone, a positive linear relation was noted by increased NIF treatment dosages in all gingival dimensions at week 6. But, this relationship was not found in the combined therapies. By histometry, tissue dimensions increased following single drug therapy, either CsA or NIF, at both levels. In animals with the combined therapies, the tissue dimensions decreased if the animals received 10 mg NIF, while they rebounded to control levels with the 50 mg dosage. A dose-dependent positive pattern by NIF was noted in tissue dimensions, but the pattern did not occur in animals that received combined therapy.


CONCLUSIONS
The gingival dimensions increased after CsA or NIF therapy, although they were more prevalent with CsA. But the augmenting pattern in gingival morphology observed with CsA therapy decreased when the animals received additional NIF. Therefore, we question whether NIF is a critical factor in aggravating the CsA-induced gingival overgrowth.
Chiu
H C
HC
Department of Periodontology, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Fu
E
E
Chiang
C Y
CY
Liu
D
D
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D003743:Dental Enamel / Q000473:pathology; D003804:Dentin / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013223:Statistics as Topic; D014092:Tooth Root / Q000473:pathology
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009543:Nifedipine