Treatment with a PPAR-γ Agonist Protects Against Hyperuricemic Nephropathy in a Rat Model

• Published in: Drug design, development and therapy development and therapy, 2020-01, Vol.14, p.2221-2233
• Main Authors: Wang, Xin, Deng, Jin, Xiong, Chongxiang, Chen, Haishan, Zhou, Qin, Xia, Yue, Shao, Xiaofei, Zou, Hequn
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Disease Models, Animal; epithelial-to-mesenchymal transition; Hyperuricemia - drug therapy; hyperuricemic nephropathy; inflammation; Kidney Diseases - drug therapy; Male; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Original Research; peroxisome proliferator-activated receptor-gamma; PPAR gamma - agonists; Rats; Rats, Sprague-Dawley; renal fibrosis; rosiglitazone; Rosiglitazone - administration & dosage; Rosiglitazone - pharmacology
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S247091

Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved. An HN rat model was established by oral administration of a mixture of adenine and potassium oxonate daily for 3 weeks. Twenty-four rats were divided into 4 groups: sham treatment, sham treatment plus RGTZ, HN, and HN treated with RGTZ. Administration of RGTZ effectively preserved renal function, decreased urine microalbumin, and inhibited interstitial fibrosis and macrophage infiltration in a rat HN model. RGTZ treatment also inhibited TGF-β and NF-κB pathway activation, decreased expression of fibronectin, collagen I, α-SMA, vimentin, MCP-1, RANTES, TNF-α, and IL-1β, and increased E-cadherin expression in the kidneys of HN rats. Furthermore, RGTZ treatment preserved expression of OAT1 and OAT3 in the kidney of HN rats. RGTZ attenuates the progression of HN through inhibiting TGF-β signaling, suppressing epithelial-to-mesenchymal transition, reducing inflammation, and lowering serum uric acid levels by preserving expression of urate transporters.