AZOLE ANTIFUNGALS - WEAK INHIBITORS NITRIC-OXIDE SYNTHASE IN MOUSE AND HUMAN-CELLS

The effect of three azole antifungals on inducible nitric oxide (iNOS) activity in different mouse and human cells was evaluated. The iNOS a ctivity was determined by L-citrulline and nitrite measurement. In the murine macrophage cell line RAW 264.7, in mouse peritoneal macrophage s (MPM) and in human colorectal adenocarcinoma cells (DLD-1), iNOS act ivity could be induced with lipopolysaccharides and cytokines. Under s imilar conditions, no iNOS induction was found in human monocytes/macr ophages. The concentration of itraconazole, ketoconazole or miconazole needed to inhibit iNOS activity by 50% in RAW 264.7 cells, MPM and DL D-1 cells was greater than or equal to 10 mu mol l(-1). This is at lea st 100 times more than the concentrations of these azole antifungals r equired to produce a 50% inhibition of yeast growth and ergosterol syn thesis of, for example, Candida albicans after the same incubation per iod. These results show that azole antifungals are weak inhibitors of iNOS in intact cells.