Nephro-protective effect of Daphnetin in hyperoxaluria-induced rat renal injury via alterations of the gut microbiota.

It is well proved that hyperoxaluria induces the renal injury and finally causes the end stage kidney disease. Daphnetin (coumarin derivative) already confirmed renal protective effect in renal model, but hyperoxaluria protective effect still unexplore. The objective of this research was to scrutinize the renal protective effect of daphnetin against ethylene glycol (GC)-induced hyperoxaluria via altering the gut microbiota. GC (1% v/v) was used for the induction of hyperoxaluria in the rats and the rats were received the oral administration of daphnetin (5, 10 and 15 mg/kg). The body and renal weight were assessed. Urine, renal, inflammatory cytokines, antioxidant, inflammatory parameters, and gut microbiota were appraised. Daphnetin effectually improved the body weight and reduced the renal weight. Its also remarkably boosted the magnesium, calcium, citrate level and suppressed the level of uric acid and oxalate formation. Daphnetin significantly (p < .001) ameliorate the level of urinary kidney injury molecule 1 (KIM-1), blood urea nitrogen (BUN), urea, serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and uric acid along with inflammatory cytokines and inflammatory mediators. Daphnetin considerably repressed the malonaldehyde (MDA) level, protein carbonyl and improved the level of glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). Daphnetin treatment considerably altered the microbial composition of different bacteria at phylum, genus and family level. Daphnetin significantly suppressed the Firmicutes relative abundance and boosted the Bacteroidetes relative abundance. Our result clearly indicated that daphnetin remarkably ameliorates the GC induced hyperoxaluria in rats via altering the oxidative stress, inflammatory reaction and gut microbiota. PRACTICAL APPLICATION: Nephrotoxicity is a serious health disease worldwide. We induce the renal toxicity in the experimental rats using the ethylene glycol and scrutinized the renal protective effect of daphnetin. Daphnetin considerably suppress the renal, urine parameters. For estimation the underlying mechanism, we estimated the gut microbiota in all group rats. Daphnetin remarkably altered the level of gut microbiota and suggesting the renal protective effect.