Jpn. J. Pharmacol. 85 (1), 84-91 (2001)

Suppression of Gingival Inflammation Induced by Porphyromonas gingivalis in Rats by Leupeptin

Sizuo Kitano1,*, Kenji Irimura2, Toru Sasaki1, Naoko Abe3, Atsuyo Baba3, Yoichiro Miyake4,
Nobuhiko Katunuma5 and Kenji Yamamoto3

1Pharmacology Research Laboratory, 2Drug Safety Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuo, Hiraishi,Kawauchi-cho, Tokushima 771-0194, Japan
3Department of Pharmacology, Faculty of Dentistry, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
4Department of Microbiology, Tokushima University School of Dentistry, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan
5Institute for Health Sciences, Tokushima Bunri University, 180, Bouji, Nisihama, Yamashiro-cho, Tokushima 770-8514, Japan
*Corresponding author. FAX: +81-88-665-6554

Abstract: In this study, we developed a procedure to produce gingivitis in rats by inoculation of Porphyromonas gingivalis and studied the contribution of the bacterial cysteine proteinases, Arg-gingipain (Rgp) and Lys-gingipain (Kgp), to the pathology in the gingiva. To adhere the bacterium to periodontal tissues, a cotton thread was inserted between the first and second molar of right maxillary sites of rats. Rats in group A were administered with vehicle alone after bacterial (strain W83) inoculation. In group B, the bacteria were inoculated in combination with leupeptin, a potent inhibitor of Rgp and Kgp, and then leupeptin alone was administered the week after. Rats in group C were administered leupeptin for 6 weeks after bacteria inoculation. All left maxillary gingiva in three groups showed no inflammatory changes. Right maxillary gingiva of group A showed most of the clinical landmarks of gingivitis. Leupeptin exhibited only a little inhibitory effect on this gingivitis in group B, whereas it had a strong inhibitory effect on the inflammation in group C. These results suggest that P. gingivalis-induced gingivitis is attributable to Rgp and Kgp and that leupeptin is more effective in the late phase than the early stage of gingivitis.

Keywords: Arg-gingipain, Lys-gingipain, Gingivitis, Leupeptin, Porphyromonas gingivalis

Copyright The Japanese Pharmacological Society

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