Coral Hydrate improves renal fibrosis by inhibiting indoxyl sulfate-induced ROS-mediated NLRP3 inflammasome...

Chronic kidney disease (CKD) is a global kidney disease characterized by chronic inflammation, oxidative stress and fibrosis in the kidney. A hydrogenated coral material known as coral hydrate (CH) has potent antioxidant activity. However, the effect of CH on renal fibrosis is rarely explored. This study aims to determine the effects of CH on renal fibrosis and indoxyl sulfate (IS)-induced renal cell injury and to elucidate the mechanisms underlying such effects. In vivo unilateral ureteral obstruction (UUO) mouse model, our findings showed that UL-CH group (UUO mice administered with low-dose CH) or UH-CH group (UUO mice administered with high-dose CH) significantly ameliorated renal fibrosis, reduced the levels of collagen I, α-smooth muscle actin (α-SMA), vimentin, Snail and Slug in renal tissues in addition to decreasing the levels of NLRP3, cleaved (c)-caspase-1, and c-IL-1β. In NRK-52E cells, CH downregulated IS-induced NLRP3, c-caspase-1, and c-IL-1β. CH treatment resulted in decreased ROS, HO-1, and p-NRF2 induced by IS stimulation, and combination treatment with CH and the NLRP3 inhibitor MCC950 further reduced NLRP3 inflammasome to levels lower than those with CH treatment alone. Collectively, these results indicate that CH has the potential to ameliorate NLRP3 inflammasome-mediated renal fibrosis.