Background and Objective: Fasting decreases urinary urate (UA) excretion by half in uricase (Uox) - knockout (KO) mice, an animal model of hyperuricemia. We speculated that rodents are heavily influenced by dietary purine intake. However, there are no reports on the differences in purine content in animal diets or their effects on UA kinetics. In this study, we measured the purine content in standard and purified diets to investigate the effect of a purified diet on UA kinetics in high hypoxanthine phosphoribosyltransferase (HPRT) - activity Uox - KO mice.
Methods: The purine contents of a standard diet, Charles River Formula-1 (CRF-1), and a purified diet, AIN93M, were measured using a peak-shift assay with xanthine oxidase (XO) treatment and HPLC. Wild-type (WT) and high HPRT-activity Uox - KO mice were fed the CRF-1 or AIN93M diet for seven days to evaluate the effects of dietary purine intake on UA-related parameters.
Results: The purine content of AIN93M was approximately one-seventeenth times lower than that of CRF-1. The WT mice showed no significant variation in UA-related parameters in the AIN93M group compared with that in the CRF-1 group; however, the urinary allantoin/creatinine ratio was decreased. Conversely, the AIN93M group showed significantly decreased plasma UA levels and urinary UA/creatinine ratios than those in the CRF-1 group of high HPRT-activityUox - KO mice.
Conclusion: High HPRT-activity Uox - KO mice were useful for evaluating the variation in UA kinetics induced by dietary therapy. Additionally, a low-purine diet decreased plasma UA levels and urinary UA excretion in a mouse model of hyperuricemia.
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