5-Bromocytidine protects against hyperuricemia-induced renal injury by suppressing TLR4/NF-κB-mediated inflammation.

Hyperuricemia (HUA), a prevalent metabolic disorder, is an independent risk factor for chronic kidney disease (CKD). Elevated serum uric acid (UA) level leads to renal UA deposition, causing kidney inflammation, impairing renal function, and accelerating HUA progression. In this study, an inflammation model in RAW264.7 cells induced by monosodium urate (MSU) was established to screen for compounds resistant to MSU-induced inflammation. Fortunately, 5-bromocytidine, a nucleic acid analogue, demonstrated potent anti-inflammatory activity in MSU-treated RAW264.7 cells and exhibited excellent therapeutic effects in HUA rats by reducing serum UA, creatinine (CRE) and blood urea nitrogen (BUN) amounts. Furthermore, we found that 5-bromocytidine blocked the activation of TLR4/NF-κB signaling pathway which mediated inflammation, and downregulated the expression of IL-1β and NLRP3. In summary, 5-bromocytidine may ameliorate HUA by suppressing the renal TLR4/NF-κB signaling pathway, suggesting a new candidate compound for HUA therapy.