Nafamostat mesilate, a potent tryptase inhibitor, modulates periodontitis in rats.
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 dimethansulfonate) on the development of experimental periodontitis 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.
Holzhausen
Marinella
M
Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil. marinella@usp.br
Balejo
Rodrigo D P
RD
Lara
Guilherme M
GM
Cortelli
Sheila C
SC
Saad
Wilson A
WA
Cortelli
José R
JR
D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D001550:Benzamidines; D001586:Benzoylarginine Nitroanilide; D002465:Cell Movement / Q000187:drug effects; D002863:Chromogenic Compounds; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D005891:Gingivitis / Q000517:prevention & control; D006098:Granulocytes / Q000187:drug effects; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D008336:Mandibular Diseases / Q000517:prevention & control; D008963:Molar / Q000187:drug effects; D010447:Peptide Hydrolases / Q000032:analysis; D010518:Periodontitis / Q000517:prevention & control*; D009195:Peroxidase / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000032:analysis; D013997:Time Factors; D014361:Trypsin Inhibitors / Q000627:therapeutic use*; D053802:Tryptases / Q000037:antagonists & inhibitors*
D001550:Benzamidines; D002863:Chromogenic Compounds; D006146:Guanidines; D044464:Receptor, PAR-2; D014361:Trypsin Inhibitors; D001586:Benzoylarginine Nitroanilide; D009195:Peroxidase; D010447:Peptide Hydrolases; D053802:Tryptases; C032855:nafamostat
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