Effects of ChondroT on potassium Oxonate-induced Hyperuricemic mice: downregulation of xanthine oxidase and urate transporter 1复制标题

软骨素对氧酸钾诱导的高尿酸血症小鼠的影响: 黄嘌呤氧化酶和尿酸转运蛋白1的下调

In the present study, we demonstrated that ChondroT, a new complex herbal medication reduced serum UA in hyperuricemic mice by downregulating XOD activity and renal mURAT1. Because XOD and URAT1 are important targets to regulate hyperuricemia and gout, potassium oxonate-induced hyperuricemic mice were used as appropriate experimental models for investigating the mechanism underlying hyperuricemia. XOD plays an important role in the catabolism of purines. The XOD enzyme catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to UA. AP, an XOD inhibitor has been used as an anti-hyperuricemia agent and anti-gout In addition, febuxostat is a novel orally administered antihyperuricemic drug that reduces the production of UA in the body by XOD inhibition. We demonstrated that ChondroT inhibited XOD activity in vitro (Table 3). PO-treated mice can serve as a useful animal model for investigating hyperuricemia pathology. The intraperitoneal administration of 300 mg/kg PO for 7 days to mice increased the serum UA, decreased the urinary UA, and elevated the serum and liver XOD activity (Figs. 1 and 2). ChondroT significantly reduced the serum UA level, whereas it increased the urinary UA level in hyperuricemic mice (Fig. 1). Moreover, the ChondroT-treated mice showed a significant decreased in serum and liver XOD activity compared with that of the hyperuricemic mice (Fig. 2). Thus, the in vivo enzyme inhibitory activity of ChondroT is the net inhibitory activity of both XOD and xanthine dehydrogenase (XDH). Hyperuricemia is frequently observed in patients with chronic kidney disease and can be accompanied by an increase in serum Cr and BUN. Previous other studies reported that AP significantly blocked renal functional changes in PO-induced hyperuricemic rats and lowered Cr levels as well as UA in patients. We demonstrated that ChondroT significantly reduced the serum Cr and BUN levels in hyperuricemic mice (Table 4). Furthermore, liver dysfunction, poor blood flow in the liver and raised uric acid may cause hyperuricemia. In this study, PO-induced hyperuricemic mice increased liver damages by increasing the levels of two markers for liver damages, GOT, and GPT, which was attenuated by ChondroT and AP.

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