Febuxostat attenuates chronic kidney disease induced by adenine in rats: role of TLR4/NF-κB/NLRP3/Caspase1/IL-1β pathway.

Chronic kidney disease (CKD) is a top public health priority and global health concern. Owing to the buildup of toxins and the decreased removal of inflammatory mediators, the illness frequently causes inflammation, which eventually impairs kidney function. This study sought to provide insight into the potential prophylactic effect of febuxostat against adenine-induced CKD. Rats were distributed into 4 groups; normal, adenine (200 mg/kg, orally, once daily) and febuxostat groups (rats received either 5 or 15 mg/kg of febuxostat concurrently with adenine). Febuxostat effectively attenuated adenine-induced CKD as manifested by marked drop in serum creatinine, BUN, proteinuria and rise in creatinine clearance. Histopathological analysis supported these biochemical results. Moreover, reduced MDA and increased GSH levels indicate that febuxostat restored the oxidant/antioxidant equilibrium. Additionally, febuxostat in both doses reduced inflammation as evidenced by reduced renal expression of TLR4 and NF-κB besides reduced renal levels of NLRP3, Caspase1, IL-1β and TNF-α. Collectively, febuxostat efficiently attenuated adenine-induced CKD via down-regulating TLR4/NF-κB/NLRP3/Caspase1/IL-1β signaling pathway. Thus, febuxostat could be beneficial in clinical use against CKD pending further analysis.