Abstract
The kidney was recognized as a dominant organ for uric acid excretion. The main aim of the study demonstrated intestinal tract was an even more important organ for serum uric acid (SUA) lowering. Sprague-Dawley rats were treated normally or with antibiotics, uric acid, adenine, or inosine of the same molar dose orally or intraperitoneally for 5 days. Rat’s intestinal tract was equally divided into 20 segments except the cecum. Uric acid in serum and intestinal segment juice was assayed. Total RNA in the initial intestinal tract and at the end ileum was extracted and sequenced. Protein expression of xanthine dehydrogenase (XDH) and urate oxidase (UOX) was tested by Western blot analysis. The effect of oral UOX in lowering SUA was investigated in model rats treated with adenine and an inhibitor of uric oxidase for 5 days. SUA in the normal rats was 20.93±6.98 μg/ml, and total uric acid in the intestinal juice was 308.27±16.37 μg, which is two times more than the total SUA. The uric acid was very low in stomach juice, and attained maximum in the juice of the first segment (duodenum) and then declined all the way till the intestinal end. The level of uric acid in the initial intestinal tissue was very high, where XDH and most of the proteins associated with bicarbonate secretion were up-regulated. In addition, SUA was decreased by oral UOX in model rats. The results suggested that intestinal juice was an important pool for uric acid, and intestinal tract was an important organ for SUA lowering. The uric acid distribution was associated with uric acid synthesis and secretion in the upper intestinal tract, and reclamation in the lower.
Highlights
Uric acid is the final product of purine nucleoside metabolism by xanthine dehydrogenase (XDH, EC 1.17.1.4) in humans
The results suggested that intestinal juice is a very important pool for uric acid distribution, even more important than serum
The results suggested that adenine and inosine by oral adminsitration were able to increase the serum uric acid (SUA), but absolutely or relatively decreased the uric acid distribution in the intestinal juice
Summary
Uric acid is the final product of purine nucleoside metabolism by xanthine dehydrogenase (XDH, EC 1.17.1.4) in humans. The level of uric acid is well controlled mainly by the balance between production from purine nucleosides in liver and excretion into urine through kidneys [1,2]. Intestinal tract is an important organ for lowering serum uric acid in rats role is poorly understood, due to its antioxidant activity, uric acid is thought to protect neuronal cells and play a role in maintaining the blood pressure [3]. Uric acid is almost insoluble in water, and forms precipitates (tophi) in the peripheral and terminal tissues or organs like kidneys, joints, and ear lobes. It is suggested that serum uric acid (SUA) levels should be kept below 7 mg/dL (about 420 μmol/L) to prevent hyperuricemia [4]. Increased SUA is an important clinical risk factor for gout, chronic kidney disease (CKD) [5,6,7,8], and some chronic cardiovascular diseases [9]
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