Loganetin protects against rhabdomyolysis-induced acute kidney injury by modulating the toll-like receptor 4 signalling pathway

Acute kidney injury (AKI) is a rapid renal dysfunctional disease, for which no effective drugs or therapies are available to improve prognosis. Loganetin is a natural product with unknown bioactivities. Here, we identified a new protective effect and mechanism of Loganetin in a mouse model of AKI induced by rhabdomyolysis. Experimental approach: AKI was induced using glycerol by i.m. injection in mice models. Thirty minutes and 24 and 48 hr after injection of glycerol, the mice received 2 and 18 mg·kg-1 of Loganetin i.p. respectively. Then mice blood and kidney were collected for various biochemical and histopathological studies. Mechanistic studies on modulation of AKI by Loganetin were performed using HK-2 cells and Toll-like receptor 4 (TLR4) knockout mice. Key

Acute kidney injury (AKI) is a rapid renal dysfunctional disease, for which no effective drugs or therapies are available to improve prognosis. Loganetin is a natural product with unknown bioactivities. Here, we identified a new protective effect and mechanism of Loganetin in a mouse model of AKI induced by rhabdomyolysis. Experimental approach: AKI was induced using glycerol by i.m. injection in mice models. Thirty minutes and 24 and 48 hr after injection of glycerol, the mice received 2 and 18 mg·kg-1 of Loganetin i.p. respectively. Then mice blood and kidney were collected for various biochemical and histopathological studies. Mechanistic studies on modulation of AKI by Loganetin were performed using HK-2 cells and Toll-like receptor 4 (TLR4) knockout mice. Key

In the Loganetin treated group, kidney damage and mortality rate were declined, and blood urea nitrogen and serum creatinine were much lower. Loganetin prevented damage to the tubular structures induced by glycerol and decreased apoptotic cells at the corticomedullary junction. In HK-2 cells, Loganetin could inhibit NF-κB pathway and pro-apoptotic genes expression. However, TLR4 was silenced by a specific shRNA, and the inhibitory effect of Loganetin in HK-2 cells vanished. Loganetin also down-regulated the expression of inflammation factors by suppressing TLR4 activity.