Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2025 Jan 9

PMID 39780982

Authors

Lina Xue

Qianru Tao

Haining Chang

Shu Yan

Lei Wang

Zefang Zhao

Chao Tu

Affiliations

Soon will be listed here.

Abstract

Purpose: Serum uric acid (SUA) is primarily produced through the hydrolysis of purines in the liver, with its excretion largely handled by the kidneys. Urate transporter 1 (URAT1) inhibitors are known to enhance uric acid elimination via the kidneys, but they also increase the risk of kidney stone formation. Currently, xanthine oxidase (XO) inhibitors are the predominant uric-lowering medications on the market.

Methods: In this study, we utilized single-cell RNA sequencing, spatial metabolomics, plasma metabolomics, flow cytometry to explore the effects of Tigulixostat on uric acid level and hyperuricemic nephropathy (HN) in Uox-KO mouse model.

Results: In this study, we discovered that Tigulixostat (LC350189) more effectively reduced SUA levels and resulted in better renal outcomes compared to allopurinol, without inducing liver injury in urate oxidase knockout (Uox-KO) mice. Mechanistically, we found that Tigulixostat improved HN by promoting M2 macrophage polarization.

Conclusion: These findings suggest Tigulixostat as a promising therapeutic option for managing hyperuricemia and related kidney conditions.

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