ABSTRACT
Gout is a common disease in the elderly men. The prevalence rate of gout is rising worldwide in recent years,and gout has become a serious metabolic disease threatening human health. Moreover,gout is also closely related to incidence of many dis?eases and symptoms such as hypertension,hyperlipidemia,atherosclerosis,obesity and insulin resistance. Recently,investigation and development of new drugs have attracted increasing attention. This paper summarizes the research advances in new agents for treat?ment of gout,including the uric acid reduction drugs that target the key enzymes of purine metabolism,the drugs which target the re?nal tubular urate transporters to lower the uric acid level,the dual inhibitors of xanthine oxidoreductase(XOR)and renal tubular urate transporters,and the uricase.
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.