Guanidino compounds inhibit nitric oxide release in J774A.1 macrophages

Chronic kidney disease (CKD) has been usually associated with accumulation of some nitrogen compounds deriving from protein catabolism like creatine (CRT), creatinine (CRTN), guanidine (GN) and methylguanidine (MG) proposed as responsible of some manifestations of uremic syndrome. 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. Nitric oxide (NO) production by inducibie nitric oxide synthase (iNOS) is a crucial step both in the activation of immunoresponsive cells and in the mechanism of citotoxicity NO mediated. The aim of this study is to evaluate if some uremic toxins like CRT, CRTN, GN, MG could interfere in macrophagic immunoresponse modulating iNOS activity. Our results demonstrated that GN and MG exerted the stronger effect in inhibiting NO release; this effect was reverted by a L-ARG supplementation. Moreover macrophage co-exposure to GN and MG further enhanced the inhibitory effect on iNOS activity and expression. Our results demonstrated that, among tested compounds, GN and MG significantly affected iNOS activity and expression.