Effects of long-term cyclosporin therapy on the periodontium of rats.
BACKGROUND
The treatment of cyclosporin A triggers an early bone loss and gingival overgrowth. There is a lack of studies exploring the effects of long-term cyclosporin A therapy on alveolar bone homeostasis and gingival tissue.


OBJECTIVE
The purpose of this study was to evaluate the effects of long-term therapy with cyclosporin A on the gingival tissue and on the alveolar bone metabolism in rats.


METHODS
Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg body weight of cyclosporin A. At the end of experimental periods, animals were killed and the serum calcium (Ca(2+)) and alkaline phosphatase levels were measured in all groups. After histological processing, the oral epithelium and the connective tissue, as well as volume densities of alveolar bone (V(b)) and multinucleated osteoclasts (V(o)), were assessed at the region of the lower first molars.


RESULTS
Significant increases in the serum alkaline phosphatase were observed in those groups that received cyclosporin A therapy. After 60 and 120 days of the treatment with cyclosporin A, evident gingival overgrowth associated with a significant increase of epithelium and connective tissue was observed, as well as a decrease of the densities of bone and an increase of densities of osteoclasts. After 180 and 240 days of the treatment, there was a reduction of the gingival overgrowth associated with significant decreases of epithelium and connective tissue, as well as an increase of bone densities and a decrease of osteoclasts.


CONCLUSIONS
Within the limits of this experimental study, it can be concluded that the deleterious periodontal effects of cyclosporin A administration may be time-related side-effects.
Spolidorio
L C
LC
Department of Oral Pathology, Dental School, University of State of Sao Paulo, Rua Humaitá 1680, Caixa Postal 331, Araraquara, Sao Paulo, Brazil, CEP. lcs@foar.unesp.br
Spolidorio
D M
DM
Holzhausen
M
M
D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D016301:Alveolar Bone Loss / Q000139:chemically induced / Q000473:pathology; D000539:Alveolar Process / Q000187:drug effects*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002452:Cell Count; D003238:Connective Tissue / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects*; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D010010:Osteoclasts / Q000187:drug effects; D010519:Periodontium / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000469:Alkaline Phosphatase; D002118:Calcium