Establishment of a screening system for xanthine oxidase (XOD) inhibitors / 中国药理学通报

ABSTRACT

Aim To establish a screening system for xanthine oxidase (XOD) inhibitors. Methods The XOD activity in vitro, serum uric acid level, serum XOD activity, tissue XOD activity and the blood indexes related to liver and kidney function were determined by biochemical method, respectively. Pathological analysis was used to observe liver and kidney. Results The optimized reaction consists of 3 U . L 1 XOD and 50 u,mol . L 1 XA under pH7.4, 37 °C. for 20 min. The high throughput screening method was established for XOD inhibitors in vitro. The acute hyperuricemia models were induced by signle dose of hypoxanthine and oteracil potassium in ICR mice. In this case, the serum uric acid level had a transient elevation after inducer administered. The changes of serum uric acid levels and the area under the uric acid-time curve were used to evaluate the acute hyperuricemia mice. The chronic hyperuricemia models were selected from the ICR mice stimulated with oteracil potassium consecutively. No significant changes of XOD activities in serum and tissue, of function and pathological structure in liver and kidney were observed in both acute hyperuricemia mice and chronic hyperuricemia mice. Conclusions The high throughput screening method for XOD inhibitors in vitro and the evaluation in vivo, in acute or chronic hyperuricemia mice, respectively, are mutually verified, forming an experimental system for developing the anti-hyperuricemia drug targeting at XOD.