Ultrastructural Quantitation of Connective Tissue Changes in Phenytoin-induced Gingival Overgrowth in the Ferret

Abstract

The gingival overgrowth obtained after maintaining ferrets on PHT appeared to be due entirely to the effect of the drug, for inflammation induced by banding had no influence on the action of PHT in eliciting the overgrowth. The significant change observed was an increase in relative volume of interstitial material (ground substance) in response to PHT. Although there was no appreciable alteration in numbers of cells present in the lesion, PHT had a significant effect on the ultrastructure of fibroblasts. These cells showed a decrease in the relative volume of phagosomes, although organelles concerned with synthesis (the rough endoplasmic reticulum and Golgi zones) were not affected. This suggests that the relative increase in ground substance may reflect decreased breakdown of extracellular material within fibroblasts, while synthetic activity is maintained at a constant level. As a consequence, there is an increase in connective tissue volume--an increase which is manifested as an overgrowth.

Impaired Degradation of Matrix Collagen in Human Gingival Fibroblasts by the Antiepileptic Drug Phenytoin

“…6,21 In the present study, collagen endocytosis in HGFs was significantly suppressed by PHT stimulation, which was associated with the decreased expression of α2β1-integrin. 6,21 In the present study, collagen endocytosis in HGFs was significantly suppressed by PHT stimulation, which was associated with the decreased expression of α2β1-integrin.…”

Oral and dental diseases in a population of domestic ferrets (Mustela putorius furo)

“…) and osteoma (Girling ) have been reported before. No drug‐induced gingival overgrowth, oral ulcers, foreign bodies and sialoceles were diagnosed in any of the ferrets included in this study, although these lesions have been previously observed (Hall & Squier , Milella , Hoefer et al . , Maurer & Fox ).…”

Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling

“…Hall and Squier (1982) as well as McGaw and Porter (1988) found that fibrosis-inducing agents (phenytoin and cyclosporin) were associated with a decreased amount of phagocytosed collagen. In line with these in vivo data are in vitro observations (McCulloch & Knowles, 1993) showing that two fibrosis-inducing drugs (dilantin and nifedipine) inhibit phagocytosis of collagen-coated beads by fibroblasts.…”