Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation

Abstract

In vitro studies have demonstrated that mercaptoethylguanidine (MEG), a selective inhibitor of the inducible NO synthase (iNOS), is also effective as a scavenger of peroxynitrite (a potent cytotoxic oxidant produced by the reaction of NO and superoxide). In the present study, we evaluated the antiinflammatory potential of MEG treatment in two models of acute inflammation (carrageenan-induced paw edema and pleurisy), where oxyradicals, NO, and peroxynitrite play a crucial role in the inflammatory process. Our data show that MEG (given at 25 microg/paw in the paw edema model or 10 mg/kg in the pleurisy model) inhibits the inflammatory response (paw swelling, pleural exudate formation, mononuclear cell infiltration, histological injury) in both models. Furthermore, MEG reduced nitrite/nitrate concentrations in the exudate and reduced the activity of the inducible isoform of NO synthase in the lung ex vivo. MEG also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. Taken together, the present results demonstrate that MEG exerts potent antiinflammatory effects. Part of these antiinflammatory effects may be related to an inhibition of the expression/activity of the inducible NO synthase, another part may be related to oxyradical and peroxynitrite scavenging.