The establishment of hyperuricemia animal model is an effective way to develop and verify therapeutic drugs of hyperuricemia. However, there is currently no standard method of the establishment of hyperuricemia model rats. In the present study, we designed to establish hyperuricemia rat model using yeast extract combined with different doses of oteracil potassium and to explore the optimal dose for model establishment. Our results showed that intraperitoneal injection of yeast extract combined with 200 mg/kg oteracil potassium is an optimal dosage for the establishment of a persistent and stable hyperuricemia animal model.
Hyperuricemia is one of the increasingly common diseases, which is reported to have afflicted more than 2 million men and women in the United States alone, and is growing rapidly in China due probably to changes in dietary habits [18–19]. Hyperuricemia is associated with abnormal uric acid concentrations in the body, resulting in the deposition of urate crystals in the joints and kidneys that lead to inflammation, as well as gouty arthritis and uric acid nephrolithiasis. In addition to an increased risk of hyperuricemia and gout, excess uric acid is also related to cardiovascular disorders, nephrolithiasis and diabetes [20–26].
Two major mechanisms have been proposed for hyperucicemia in man, excess production and insufficient metabolisation of uric acid. Yeast extract paste and oteracil potassium were used to mimic both mechanisms: yeast represents excess production of UA, probably the main mechanism in man, and oteracil potassium impairs metabolisation [21, 27]. Potassium oxonate is most frequently employed to develop an animal model of hyperuricemia by inhibiting uricase that converts uric acid to allantoin. However, there exist great differences among different researchers in the type of drug compatibility, the way of drug use, the dosage and the method of animal selection and there is currently no standard method of the establishment of hyperuricemia model rats.
In the present study, serum uric acid levels were significantly increased on 7th, 14th, 21th and 28th day in the groups of intraperitoneal injection with yeast extract alone, yeast extract by intraperitoneal injection combined with 50–200 mg/kg oteracil potassium by intraperitoneal injection and yeast extract by intraperitoneal injection combined with 50–200 mg/kg oteracil potassium by intragastric feeding.
Hyperuricemia has been closely associated with renal dysfunction. High level of uric acid could increase the burden of the kidney and cause renal damage . In the present study, YE i.p. +200 mg/kg OP i.p. group developed the elevated levels of serum urea nitrogen and creatinine levels compared with NC group, and showed pathological changes of kidney, including the thickening of the glomerular wall, proliferation of some endothelial cells in glomerular capillary loop and edema of renal tubular epithelial cells, chronic inflammatory cell infiltration in the renal interstitial and urate crystal deposition and endothelial cell proliferation of renal interstitial artery and lumen stenosis (Fig. 1), which is consistent with the results of various studies, but the mechanism involved is not clear.
Purine metabolism in the circulatory system yields uric acid as its final oxidation product, which is believed to belinked to the development of gout and kidney stones. In addition, hyperuricemia is closely correlated with cardiovascular disease too. A number of epidemiologic studies have confrmed an association between hyperuricemia and CVD . A study in Japan has reported that hyperuricemia is positively associated with obesity, hypertension and dyslipidemia, and hyperuricemic subjects tend to have a clustering of these cardiovascular risk factors. In the present study, we found morphological and pathological changes in heart, thoracic aorta and femoral artery in the YE i.p.+200 mg/kg OP i.p. group, indicating that intraperitoneal injection of yeast extract combined with 200 mg/kg oteracil potassium is an optimal dosage for the construction of a hyperuricemia animal model with pathological damages related to secondary cardiovascular diseases.