Methylguanidine (MG) is a nitrogen compound deriving from protein catabolism that accumulates in Chronic kidney disease (CKD). Changes in monocyte functions have been recognised as one of the most important key factor responsible for the immunological disorders associated with uremia and it has been demonstrated that high blood concentrations of nitrogen compounds, as MG, could be responsible of immunodisfunctions associated to uremic syndrome. Inducibie nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) and their respective metabolites, nitric oxide and prostaglandins, are a crucial step both in the activation of immunoresponsive cells and in the mechanism of citotoxicity, NO mediated. It has been previously reported the ability of MG to inhibit iNOS activity and expression both in vitro and in vivo. The aim of this study is to evaluate if MG could interfere with macrophagic immunoresponses also modulating iNOS and COX-2 at different time of incubation in J774A.1 stimulated with Lipopolysahharide from E.coli. Our results demonstrated that MG exerted inhibitory effect on iNOS and COX-2. These effects are related to incubation time thus highliting the detrimental effect of immune system by MG in uremic conditions.

Time related inhibition by methylguanidine in LPS-stimulated J774A.1 macrophages

MARZOCCO, STEFANIA;AUTORE, Giuseppina
2013

Abstract

Methylguanidine (MG) is a nitrogen compound deriving from protein catabolism that accumulates in Chronic kidney disease (CKD). Changes in monocyte functions have been recognised as one of the most important key factor responsible for the immunological disorders associated with uremia and it has been demonstrated that high blood concentrations of nitrogen compounds, as MG, could be responsible of immunodisfunctions associated to uremic syndrome. Inducibie nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) and their respective metabolites, nitric oxide and prostaglandins, are a crucial step both in the activation of immunoresponsive cells and in the mechanism of citotoxicity, NO mediated. It has been previously reported the ability of MG to inhibit iNOS activity and expression both in vitro and in vivo. The aim of this study is to evaluate if MG could interfere with macrophagic immunoresponses also modulating iNOS and COX-2 at different time of incubation in J774A.1 stimulated with Lipopolysahharide from E.coli. Our results demonstrated that MG exerted inhibitory effect on iNOS and COX-2. These effects are related to incubation time thus highliting the detrimental effect of immune system by MG in uremic conditions.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4134453
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