Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger, on production of nitric oxide in RAW 264.7 macrophages

As well as superoxide generated from neutrophils, nitric oxide (NO) produce d by inducible nitric oxide synthase (iNOS) in macrophages plays an importa nt role in inflammation, We previously showed that 6-formylpterin, a xanthi ne oxidase inhibitor, has a superoxide scavenging activity. In the present study, to elucidate other pharmacological activities of 6-formylpterin, we investigated the effects of 6-formylpterin on production of nitric oxide (N O) in the murine macrophage cell line RAW 264.7 stimulated by lipopolysacch aride (LPS) and interferon-gamma (INF-gamma). 6-Formylpterin suppressed the expression of iNOS, and it also inhibited the catalytic activity of iNOS, which collectively resulted in the inhibition of NO production in the stimu lated macrophages. However, 6-formylpterin did not scavenge the released NO from an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). These results in dicate that 6-formylpterin inhibits pathological NO generation from macroph ages during inflammation, but that it does not disturb the physiological ac tion of NO released from other sources. (C) 2000 Elsevier Science B.V. All rights reserved.