Abstract

ObjectiveHyperuricemia is an important risk factor for renal diseases and contributes to renal fibrosis, and it's a big challenge for clinic. Phloretin, a plant‐derived dihydrochalcone, has shown antioxidant/anti‐inflammatory properties, and could inhibit uric acid (UA) uptake in vitro, but its role on renal injury remains unknown. In this study, we aimed to investigate the therapeutic potential of phloretin on hyperuricemia‐induced renal dysfunction and underlying mechanism in mice.MethodsMice were induced hyperuricemic by oral gavage of adenine/potassium oxonate mixture, and then treated with phloretin. The effects of phloretin on renal function, inflammation and interstitial fibrosis were evaluated in hyperuricemic mice. The changes of renal mitochondrial oxidative stress and UA metabolism were also analyzed.ResultsHyperuricemic mice showed renal dysfunction with elevated renal inflammation and fibrosis. By contrast, phloretin significantly improved renal function and morphologic lesions, as indicated by reduced levels of serum blood urea nitrogen (BUN), creatinine and urinary albumin to creatinine ratio (UACR), as well as decreased levels of kidney tubular necrosis, interstitium extracellular matrix (ECM) deposition and interstitial fibroblasts activation in the kidneys of hyperuricemic mice. Furthermore, phloretin significantly suppressed renal mitochondrial reactive oxygen species (ROS) production and NOD‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling, and inhibited glucose transporter 9 (GLUT9) and UA reabsorption in hyperuricemic mice.ConclusionPhloretin can ameliorate hyperuricemia‐induced chronic renal injury through co‐inhibiting NLRP3 pathway and UA reabsorption, and thus it might be a promising therapy to hyperuricemia‐related renal diseases.Support or Funding InformationThis work was supported by grants from National Natural Science Foundation of China (31200754, 81571808, 31871001) and China Postdoctoral Science Foundation (2012M511931).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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