An Involvement of Granulocyte Medullasin in Phenytoin-Induced Gingival Overgrowth in Rats

• Published in: Japanese Journal of Pharmacology Vol. 89; no. 3; pp. 235 - 241
• Main Authors: Ozaki, Yukio, Kunimatsu, Kazushi, Hara, Yoshitaka, Kato, Ihachi, Aoki, Yosuke, Yamamoto, Kenji, Kato, Yuzo
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Pharmacological Society 2002
• Subjects: Animals; Gingiva - chemistry; Gingiva - drug effects; Gingiva - metabolism; Gingival Hyperplasia - chemically induced; Gingival Hyperplasia - metabolism; Gingival overgrowth; Granulocytes - chemistry; Granulocytes - drug effects; Granulocytes - metabolism; Immunohistochemistry; Male; Medullasin; Phenytoin; Phenytoin - pharmacology; Rats; Rats, Inbred F344; Serine Endopeptidases - analysis; Serine Endopeptidases - biosynthesis; Serine proteinase
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.89.235

To investigate the relationship between histological changes and distributions of medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced gingival overgrowth, we established a rat model of gingival overgrowth. Thirty-two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet, but without the drug and killed at the same weeks as experimental rats (n = 32) and 0 week (n = 8). The mandible specimens were resected and sectioned bucco-lingually between the first and second molars. A marked inflammatory-cell infiltration and elongated rete pegs were seen in the phenytoin-treated group. The extent of the overgrowth assessed by computer image analysis and the density of medullasin-positive cells by immuno-histochemistry in the approximal gingiva showed a significant increase in the phenytoin-treated group compared to the control group. A marked infiltration of the positive cells in experimental rats was observed as early as 2 weeks when gingival overgrowth was not fully established. Medullasin-positive cells were mostly neutrophils and partly macrophage-like cells. These findings suggest that medullasin may be involved in mainly host defense and secondarily collagen metabolism in the phenytoin-induced rat model of gingival overgrowth.