Whey protein peptide PEW attenuates hyperuricemia and associated renal inflammation in potassium oxonate and hypoxanthine-induced rat

Pro-Glu-Trp (PEW), a whey protein-derived peptide, has been previously shown in vitro to have anti-hyperuricemic potential. The current study further evaluated the roles and the underlying mechanism of PEW in the management of hyperuricemia (HUA) in rat induced by potassium oxonate (PO) and hypoxanthine. Results revealed that PEW significantly reduced the levels of uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN) in serum, and effectively suppressed the activities of xanthine oxidase (XOD) associated with UA synthesis and modulated the expression of organic ion transporters related to UA excretion. Moreover, PEW alleviated UA-induced renal inflammation by regulating oxidative stress, suppressing the level of pro-inflammatory cytokines, and inhibiting the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB (TLR4/MyD88/NF-κB) signaling pathway. Taken together, these relults indicated that PEW improved HUA and renal inflammation by inhibiting UA synthesis, promoting renal UA excretion and suppressing NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways.