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. 2021 Jul 14:12:667753.
doi: 10.3389/fphar.2021.667753. eCollection 2021.

Function of Uric Acid Transporters and Their Inhibitors in Hyperuricaemia

Affiliations

Function of Uric Acid Transporters and Their Inhibitors in Hyperuricaemia

Hao-Lu Sun et al. Front Pharmacol. .

Abstract

Disorders of uric acid metabolism may be associated with pathological processes in many diseases, including diabetes mellitus, cardiovascular disease, and kidney disease. These diseases can further promote uric acid accumulation in the body, leading to a vicious cycle. Preliminary studies have proven many mechanisms such as oxidative stress, lipid metabolism disorders, and rennin angiotensin axis involving in the progression of hyperuricaemia-related diseases. However, there is still lack of effective clinical treatment for hyperuricaemia. According to previous research results, NPT1, NPT4, OAT1, OAT2, OAT3, OAT4, URAT1, GLUT9, ABCG2, PDZK1, these urate transports are closely related to serum uric acid level. Targeting at urate transporters and urate-lowering drugs can enhance our understanding of hyperuricaemia and hyperuricaemia-related diseases. This review may put forward essential references or cross references to be contributed to further elucidate traditional and novel urate-lowering drugs benefits as well as provides theoretical support for the scientific research on hyperuricemia and related diseases.

Keywords: gene; hyperuricaemia; inhibitor; transporters; uric acid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mainly physiological progression of uric acid in the body. Serum uric acid is original from uptake of foods containing a high level of purines as well as catabolism of proteins and other compounds in the human body. About 60% uric acid involves in metabolism process and the rest of uric acid is excreted through the gut and urethra. Urethral excretion is the main way. A series of urate transporters including SLC and ABC transporters expressed in urethra, especially the proximal convoluted tubules, maintain urate homeostasis.
FIGURE 2
FIGURE 2
Urat-lowering drugs in hyperuricaemia-related diseases. Hyperuricaemia has been proven to be associated with multiple diseases including gout, chronic kidney disease, cardiovascular diseases, metabolic syndrome. The discovery of urate transporters provides new ideas for the development of drugs for the research of hyperuricaemia. In addition to urate transport inhibitors, xanthine oxidase inhibitors, SGLT2 inhibitors, as well as novel urat-lowering drugs like EEAK, Favipiravir, PF-06743649 have been summarized.

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