ORIGINAL ARTICLE Nafamostat mesilate, a potent tryptase inhibitor, modulates periodontitis in rats Marinella Holzhausen & Rodrigo D. P. Balejo & Guilherme M. Lara & Sheila C. Cortelli & Wilson A. Saad & José R. Cortelli Received: 22 April 2010 / Accepted: 25 August 2010 / Published online: 5 September 2010 # Springer-Verlag 2010 Abstract Previous reports have demonstrated increased tryptase-like proteolytic activity in the crevicular fluid of patients with periodontal disease. In the present study, we have investigated the effect of tryptase inhibition with nafamostat mesilate (NM, 6-amino-2-naphtlyl p-guanidinobenzoate dime- thansulfonate) on the development of experimental periodon- titis in rats. Eighty (80) male Wistar rats were randomly separated into four groups: Control group, NM group (daily 0.1 mg/kg body weight of NM, i.p.), Ligature group (ligature placed at lower right first molars), and NM+Ligature group. The amount of alveolar bone loss (ABL) around the mesial root surface of the first mandibulary molar, as well as the myeloperoxidase (MPO) activity, and total proteolytic activity [N-benzoyl-L-arginine-p-nitroanilide (BApNA) substrate] were determined at 7 and 14 days. NM led to significantly (p <0.05) decreased ABL in animals subjected to ligature- induced periodontitis. Tryptase inhibition prevented the onset of significant ABL at 7 days of experiment (0.44±0.16 and 0.60±0.22, p >0.05, NM+Ligature and Control, respectively) and significantly decreased the ABL at 14 days (0.97±0.17 versus 1.82±0.26, p <0.001, NM+Ligature versus Ligature, respectively). In addition, NM significantly decreased MPO and total proteolytic activity at 14 days (p <0.05). These data provided evidence that tryptase inhibition with NM attenuates gingival granulocyte infiltration and ABL in an experimental model of periodontitis in rats. Keywords Periodontal diseases . Tryptases . Alveolar bone loss . Rats Introduction Periodontal disease is the most important cause of tooth loss in adult population [1]. Although multifactorial, the patho- genesis of periodontitis involves the presence of a bacterial biofilm, which initiates a local inflammatory reaction in a predisposed host, therefore resulting in tissue destruction and alveolar bone loss (ABL) [2]. A number of cells and their mediators orchestrate the organized and complex periodontal immune system during the inflammatory process [3]. In all the inflammatory cascades of periodontal disease, there are some steps which are mediated by proteolytic enzymes. In fact, increased levels of proteolytic activity have been found at the gingival crevicular fluid, where a mixture of host endogenous enzymes and bacterial proteases combine each other in order to mediate connective tissue breakdown [4]. Host enzymes comprise the serine proteases like trypsin, elastase, plasmine, complement enzymes, and tryptase [5, 6]. Clin Oral Invest (2011) 15:967–973 DOI 10.1007/s00784-010-0463-1 M. Holzhausen Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil R. D. P. Balejo : G. M. Lara : S. C. Cortelli : J. R. Cortelli Department of Periodontology, Faculty of Dentistry, University of Taubaté, Taubaté, SP, Brazil W. A. Saad Department of Physiology and Pharmacology, Institute of Bioscience, University of Taubaté, Taubaté, SP, Brazil M. Holzhausen (*) Avenida Prof. Lineu Prestes, 2227, Cidade Universitária, São Paulo, SP 05508-000, Brazil e-mail: marinella@usp.br