XO activity was assessed in A) human sickle cell disease patients compared to healthy controls and B) chimeric AA control, AS sickle trait, and SS sickle mice. C) Experimental design. D) XO activity of plasma, liver, lung, and kidney after 10 weeks of febuxostat treatment. LC/MS-MS was used for purine metabolite analysis of E) hypoxanthine, F) xanthine, and G) urate. H) A CBA assay was used to measure plasma oxidant load. I) Febuxostat treatment did not alter body weight. Values are mean ± SEM using an unpaired Student’s t test unless otherwise noted. +Values are mean ± SEM using an unpaired Student’s t test with Welch’s correction. $Values are mean ± SEM using a one-way ANOVA with Dunnett’s multiple comparisons test. #Values are mean ± SEM using a Mann-Whitney test. XO, xanthine oxidase; SCD, sickle cell disease; CBA, coumarin boronate acid; WT, wild type; febux, febuxostat.