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.