Effect of xanthopterin and isoxanthopterin on nitric oxide production by a RAW264.7 cell line

Abstract

The pteridines xanthopterin (2‐amino‐4,6(3H,5H)‐pteridinedione) and isoxanthopterin (2‐amino‐4,7(3H,8H)‐pteridinedione) are products of the degradation of tetrahydrobiopterin, a coenzyme used by aryl amino acid hydroxylases, glyceryl ether monooxidase and nitric oxide synthases. These pteridines have cytotoxic effects on a number of cell lines including human mammary carcinoma MCF‐7 cell lines (Lord et al 2005, Cancer Lett. 222, 119). We wished to test the possibility that the pteridines could affect the activity of a nitric acid synthase. Accordingly, we performed experiments in which xanthopterin and isoxanthopterin were tested for their effect on nitric oxide (NO) production by a RAW264.7 mouse macrophage cell line with the resultant nitrite detected by the Griess assay. Both pteridines showed a dose‐dependent reduction of nitric oxide production with respect to controls. Whether this lowering of nitric oxide concentrations is due to inhibition of the inducible nitric oxide synthase will have to be examined. Furthermore, this finding may be significant since nitric oxide affects apoptosis (Brüne 2003, Cell Death and Differentiation 10, 864) and because of the well‐recognized association between chronic inflammation, cell proliferation, cancer and other diseases (Korhonen et al 2005 Current Drug Targets – Inflammation and Allergy 4, 471).