Establishment Of Rat Models For Screening Slow-Acting Drugs Of Hyperuricemia

Hyperuricemia, caused by dietary, environmental and genetic factors, has been recognized as a high risk factor for gout, cerebrovascular and cardiovascular diseases. Most hyperuricemic animal models were carried out on rats with short-term treatment (<1-15 days), which were not suitable for screening of agents with long-term effect and mechanisms of action, especially for traditional Chinese medicines. In this study, several combinations of two types of model drugs were adopted to establish a stable model of hyperuricemia in rats during 15-45 days. Results showed that either co-administration of adenine plus oteracil potassium or administration of toteracil potassium alone was able to increase serum uric acid levels in a time dependent manner. Allopurinol significantly decreased elevated serum uric acid levels in all models, while benzbromarone only took effect in the model using oteracil potassium alone. In addition, prominent macroscopic and microscopic abnormity of kidney were observed in adenine-treated groups and appreciably attenuated by allopurinol, which suggested that morphologic indexes or enzyme parameters regarding renal injury may have the potential to be an indicator of drug efficacy. The test platform we established based on different approaches may play an important role in screening for the majority slow-acting antihyperuricemia agents acting by different mechanisms.