title: Nafamostat mesilate, a potent tryptase inhibitor, modulates periodontitis in rats.
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 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.
authors.affiliation: Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil. marinella@usp.br
authors.forename: Marinella
authors.initials: M
authors.lastname: Holzhausen
authors.forename: Rodrigo D P
authors.initials: RD
authors.lastname: Balejo
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Lara
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Cortelli
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Saad
authors.forename: José R
authors.initials: JR
authors.lastname: Cortelli
mesh_terms: 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*
chemical_list: 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
references.citation: N Engl J Med. 1990 Feb 8;322(6):373-82
references.pmid: 2405268
references.citation: J Clin Periodontol. 2004 Jun;31(6):413-9
references.pmid: 15142208
references.citation: J Immunol. 2003 Jun 1;170(11):5690-6
references.pmid: 12759451
references.citation: Scand J Gastroenterol. 2006 Aug;41(8):944-53
references.pmid: 16803693
references.citation: J Leukoc Biol. 1997 Mar;61(3):233-45
references.pmid: 9060446
references.citation: Am J Pathol. 2006 Apr;168(4):1189-99
references.pmid: 16565494
references.citation: Trends Pharmacol Sci. 2000 Mar;21(3):103-8
references.pmid: 10689364
references.citation: Bone. 2000 Jan;26(1):7-14
references.pmid: 10617151
references.citation: Periodontol 2000. 1997 Jun;14:144-57
references.pmid: 9567969
references.citation: Crit Rev Oral Biol Med. 2003;14(3):188-98
references.pmid: 12799322
references.citation: J Periodontal Res. 1992 Jan;27(1):62-9
references.pmid: 1531511
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2003 Jul;368(1):10-6
references.pmid: 12819855
references.citation: J Clin Invest. 2003 Jan;111(1):25-7
references.pmid: 12511583
references.citation: Genes Dev. 1997 Jan 15;11(2):187-97
references.pmid: 9009202
references.citation: J Clin Periodontol. 1999 Jun;26(6):366-73
references.pmid: 10382576
references.citation: J Periodontol. 1992 May;63(5):412-7
references.pmid: 1356148
references.citation: J Immunol. 1997 Dec 15;159(12):6216-25
references.pmid: 9550425
references.citation: J Invest Dermatol. 1982 Mar;78(3):206-9
references.pmid: 6276474
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15072-7
references.pmid: 12397176
references.citation: Periodontol 2000. 2006;40:77-93
references.pmid: 16398686
references.citation: Arch Dermatol Res. 2008 Oct;300(9):461-78
references.pmid: 18719932
references.citation: J Periodontol. 2002 Sep;73(9):1030-6
references.pmid: 12296588
references.citation: Clin Rheumatol. 2007 Aug;26(8):1284-92
references.pmid: 17205215
references.citation: Infect Immun. 2001 Aug;69(8):5121-30
references.pmid: 11447194
references.citation: J Dent Res. 2005 Feb;84(2):154-9
references.pmid: 15668333
references.citation: Mem Inst Oswaldo Cruz. 2005 Mar;100 Suppl 1:177-80
references.pmid: 15962119
references.citation: Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 2):S138-42
references.pmid: 7952649
references.citation: J Periodontol. 1993 Sep;64(9):870-7
references.pmid: 7693909
references.citation: J Cell Biochem. 1992 Dec;50(4):337-49
references.pmid: 1469068
references.citation: Eur J Pharmacol. 1997 Jun 5;328(1):89-97
references.pmid: 9203574
references.citation: FEBS Lett. 1998 Sep 11;435(1):45-8
references.pmid: 9755856
references.citation: J Clin Periodontol. 1992 May;19(5):333-9
references.pmid: 1355496
references.citation: J Oral Pathol Med. 1996 Aug;25(7):376-81
references.pmid: 8890052
references.citation: Periodontol 2000. 2005;39:53-72
references.pmid: 16135064
references.citation: J Dent. 1992 Apr;20(2):90-9
references.pmid: 1348749
references.citation: Adv Dent Res. 1994 Jul;8(2):329-36
references.pmid: 7865094
references.citation: Oral Dis. 2005 Jul;11(4):249-54
references.pmid: 15984957
references.citation: J Allergy Clin Immunol. 2006 Jul;118(1):105-12
references.pmid: 16815145
references.citation: Ann Dent. 1991 Summer;50(1):25-9
references.pmid: 1714688
references.citation: Biochem J. 1996 Mar 15;314 ( Pt 3):1009-16
references.pmid: 8615752
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9208-12
references.pmid: 7937743
references.citation: Nat Med. 2001 Jul;7(7):821-6
references.pmid: 11433347
references.citation: J Orthop Res. 2005 Jul;23(4):942-8
references.pmid: 15972256