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Plasma and hepatic XO activity were measured using the pterin-based assay^[@CR40]^. Briefly, frozen liver tissues were homogenized with potassium phosphate buffer, pH 7.4, containing 1 mM EDTA and protease inhibitors. The homogenates were centrifuged at 12,000 g for 15 min at 4 °C, and supernatants were collected. Either supernatant or plasma was co-incubated with 50 μM pterin solution to assay XO activity. After 60 min incubation at 37 °C, fluorometric assays were performed to calculate the production of isoxanthopterin. Activity of purified XO derived from buttermilk (Merck KGaA) and liver tissue protein concentration were measured and used to normalize the sample activity.

UA measurement {#Sec12}
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UA levels in plasma and liver were measured as described previously, with minor modifications^[@CR41]^. Plasma samples were supplemented with 100 μM allopurinol to suppress xanthine oxidoreductase activity. Frozen liver tissues were homogenized with potassium phosphate buffer, containing 100 μM allopurinol and 1 mM potassium oxonate, to avoid synthesis and degradation of UA, and centrifuged at 20,000 g for 5 min at 4 °C. Plasma and liver homogenate was added to a mixture of water and methanol. The resulting solution was mixed thoroughly on a vortex mixer for 5 s and centrifuged for 5 min at 20,000 g at 4 °C. The supernatants were subjected to UA measurement. Plasma and liver tissue concentrations of UA were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) on a Prominence UFLC system (Shimadzu, Kyoto, Japan) using an ODP2 HP-2D column (Shodex, Tokyo, Japan). The column oven was maintained at 40 °C, the flow rate was 0.25 mL/min, and the injection volume was 2 μL (plasma) or 1 μL (liver tissue). Separation was performed using a quaternary mobile phase consisting of water/ammonium acetate (1,000:1, v/v) (50%) and methanol (50%), with a flow rate of 0.25 mL/min. Electrospray ionization tandem mass spectrometry (ESI