C57BL/6 mice that received water i.v. (H2O mice) presented marked vascular haemolysis after 15 min; levels of plasma Hb were more than doubled in H2O mice, compared to mice that receiving PBS i.v. (2.57±0.43g/dL, 1.08±0.08g/dL Hb, respectively, p<0.01, n=3-5), and resembled those of SCD mice (data not shown). In contrast, C57BL/6 mice (n=3) that received an inflammatory stimulus (TNF-α) showed no alteration in plasma free Hb levels (1.29±0.43 g/dL, 1.23±0.09 g/dL; PBS and TNF-α, respectively). IVM demonstrated that both the inflammatory and haemolytic stimuli induced leukocyte adhesion to vessel walls (3.57±0.84; 11.07±0.92; 7.25±1.20 [100µm-1] for PBS, TNF-α and H2O, respectively, p<0.05, N=15-30 venules), as well as leukocyte extravasation (1.07±0.17; 4.02±0.39; 2.97±0.49 [per 100 µm x 50 µm] for PBS, TNF-α and H2O, respectively, p<0.05, N=15-30 venules). Surprisingly, when HU was given simultaneously with TNF-α or following H2O, this drug was able to prevent leukocyte recruitment in both models, reducing both leukocyte adhesion (7.40±0.47; 2.79±0.34 [100 µm-1] for TNF-α+PBS and TNF-α+HU, respectively, p<0.0001, n=30-60 venules; and 7.84±0.73; 2.41±0.37 for H2O+PBS and H2O+HU, p<0.0001, n=20-30 venules) and leukocyte extravasation (3.88±0.26; 1.22±0.18 for TNF-α+PBS and TNF-α+HU, p<0.0001, n=30-60 venules and 2.98±0.32; 1.94±0.21 for H2O+PBS and H2O+HU, p<0.0001, n=20-30 venules) and increased leukocyte rolling (18.11±1.58; 25.48±5.01 for TNF-α+PBS and TNF-α+HU, respectively, p<0.05, n=30-60 venules and 11.56±1.47; 32.47±3.54 for H2O+PBS and H2O+HU, p<0.0001, n=20-30 venules). Additionally, DEANO was also able to reverse the inflammatory process installed by TNF-α, reducing leukocyte adhesion (10.24±1.49; 11.45±1.40 for TNF-α before and after vehicle control, n=21-22 venules; 7.63±0.63; 3.76±0.41 for TNF-α, before and after DEANO, p<0.01; n=29-35 venules) and extravasation (1.95±0.29; 3.23±0.44 before and after vehicle control, p<0.05, n=21-22 venules; 2.49±0.25; 2.24±0.24 before and after DEANO, n=29-35 venules).