title: Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic.
abstract: M40403, [manganese(II)dichloro[(4R,9R,14R,19R)-3,10,13,20,26 pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa-1(26),-22(23),24-triene]], is a low-molecular-weight, synthetic, manganese-containing superoxide dismutase mimetic that removes superoxide anions without interfering with other reactive species known to be involved in inflammatory responses (e.g., nitric oxide, NO and peroxynitrite, ONOO-). As such, M40403 represents an important pharmacological tool to dissect the roles of superoxide anion in acute and chronic inflammation. For this purpose, the pharmacological profile of M40403 was evaluated in a rat model of periodontitis. Periodontitis was induced in rats by placing a 2/0 braided silk around the lower left first molar. On day 8 the gingivomucosal tissue encircling the first molar was removed for biochemical and histological analysis. Ligation significantly increased inducible nitric oxide synthase activity and expression, and gingival tissue revealed increased neutrophil infiltration, lipid peroxidation and positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of M40403 (10 mg/kg daily for 8 days) significantly decreased all of the above-described markers of inflammation. This suggests compounds that inhibit the generation of superoxide anion, such as M40403 may be potentially useful for the treatment of periodontitis.
authors.affiliation: Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica-Policlinico Universitario Via C. Valeria-Gazzi-98100 Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Federico
authors.initials: F
authors.lastname: Rotondo
authors.forename: Francesco
authors.initials: F
authors.lastname: Dattola
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.forename: Massimo
authors.initials: M
authors.lastname: De Majo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D008026:Ligation / Q000009:adverse effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008345:Manganese; D020556:Neutrophil Infiltration / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D010518:Periodontitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; C121876:imisopasem manganese; C002744:3-nitrotyrosine; D014443:Tyrosine; D008345:Manganese; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases