ABSTRACT
OBJECTIVE: To investigate the time- and dose-dependent effects of 3, 5, 2', 4'-tetrahydroxy chalcone (P40) on the levels of uric acid and the contents of hepatic xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in the hyperuricemic mice induced by potassium oxonate. METHODS: The hyperuricemic mice were induced by an intraperitoneal injection of uricase inhibitor potassium oxonate. Serum uric acid levels were determined by using tie phosphotungstic acid method. The contents of hepatic XOD and XDH were determined using commercially available Elisa kits. Allopurinol was as a positive control. RESULTS: When orally administrated to the oxonate-induced hyperuricemic mice, compound P40 at doses of 0.5, 1.0, 2.0, 4.0 mg · kg-1 and the allopurinol at a doses of 1.0 mg · kg-1 significantly decreased the uric acid levels and reduced the concentration of XOD compared with model group. As for the study of time-dependent effects: after administration of allopurinol 30 min or P40 60 min effectively reduced serum uric acid levels compared to the model group, respectively. Administration with P40 and allopurinol for 15, 30, 60, 90 min can reduce the concentration of XDH and XOD, compared with model group. CONCLUSION: P40 could reduce the serum uric acid levels in oxonate-induced hyperuricemic mice by reducing the contents of hepatic XDH/XOD.
ABSTRACT
Aim To investigate the effects of 3 ,5 ,2 ’ , 4’-tetrahydroxychalcone (P40) on urate excretion, as well as mRNA and protein expressions of renal URAT1 and GLUT9 in hyperuricemic mice. Methods Sixty Kunming mice were randomly divided into six groups:normal control group, hyperuricemic group ( model group), P40 2. 0, 4. 0, 8. 0 mg·kg-1 groups and positive control group. All drugs were administered in-tragastrically to mice for 5 doses. Hyperuricemic mice were induced by intraperitoneal injection of uric acid (0. 15 g·kg-1 body weight) for 3 times. The urate levels were assayed with the phosphotungstic acid method. The mRNA and protein expressions of GLUT9 and URAT1 were determined by RT-PCR and Western blot. Results P40 at a dose of 4. 0 and 8. 0 mg · kg-1 significantly reduced the serum urate levels in a dose-dependent manner, when compared with untreat-ed hyperuricemic mice ( P<0. 05 or 0. 01 ) . The he-patic urate contents decreased in untreated-and treated-hyperuricemic mice as compared with normal mice ( P<0. 01 ) . Furthermore, P40 had no influence on the renal URAT1 mRNA and protein expression levels, while it could down-regulate renal GLUT9 protein ex-pression but not mRNA expression in hyperuricemic mice. Conclusion P40 possesses potent uricosuric effects associated with urate reabsorption by down-regu-lating the protein expression of GLUT9 in kidney.