Reduced development of experimental periodontitis by treatment with M40403, a superoxide dismutase mimetic.

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.

Effects of Tempol, a membrane-permeable radical scavenger, in a rodent model periodontitis.

BACKGROUND: Recent studies have demonstrated that Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a cell membrane-permeable radical scavenger, exerts protective effects in various models of inflammation and shock. Reactive oxygen species (ROS) plays a pivotal role in the induction of genes involved in physiological processes as well as in the response to inflammation. AIM: We have investigated the effect of Tempol in a rat model of periodontitis. MATERIALS AND METHODS: Periodontitis was induced in rats by placing a 2/0 braided silk ligature around the lower left first molar. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed for evaluation of neutrophils infiltration, tissue permeability, nitrotyrosine formation, poly-(ADP-ribose) polymerase (PARP) activation, radiography and histology. RESULTS AND CONCLUSIONS: Legation significantly induced an increased neutrophil infiltration and a positive staining for nitrotyrosine formation and PARP activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone erosion as evaluated by radiography analysis. Intraperitonial injection of Tempol (10 mg/kg daily for 8 days) significantly decreased all of the parameters of inflammation as described above. This suggests that antioxidant therapies, which interfere with ROS, may be of benefit in the treatment of periodontitis.