Figure 2.
MW01-5-188WH is readily detected in the plasma and the brain after a single oral dose administration and does not suppress peripheral tissue inflammatory responses or cause liver injury after chronic oral administration. C57BL/6 mice were administered MW01-5-188WH (2.5 mg/kg) by oral gavage, blood and brain processed at different times after administration, and compound levels in plasma and brain determined as described in Materials and Methods. MW01-5-188WH rapidly appears in plasma (A) and brain (B), reaches a peak at 15 min, and then slowly declines to basal levels by 120 min. Data are the mean± SEM from three to six mice at each time point. MW01-5-188WH does not inhibit increased production of IL-1β (C) and TNF-α (D) in the serum but does suppress the cytokine response in the brains from the same mice (E, F). Mice (n = 3-6 per group) were administered by oral gavage either diluent or MW01-5-188WH (2.5 mg/kg) once daily for 2 weeks and then challenged with LPS (10 mg/kg, i.p.) for 6 h. Control mice were injected with saline. IL-1β and TNF-α levels in the serum and in brain supernatants were determined. Data represent mean ± SEM. ***p < 0.001, significantly different from diluent. Daily oral administration of diluent (G) or MW01-5-188WH (H) (2.5 mg/kg) does not result in any histological liver toxicity. Representative liver sections from mice treated as in C-F were stained with hematoxylin and eosin. Scale bar, 125 μm. 188, MW01-5-188WH.