Protective Effects of Evodiamine against LPS-Induced Acute Kidney Injury through Regulation of ROS-NF-κB-Mediated Inflammation

Abstract EN

Acute kidney injury (AKI) is a critical care syndrome, which is usually associated with sepsis-related endotoxemia.

Evodiamine (EVO) is an active ingredient of many traditional medicinal formulations that possess a battery of biological activities.

In the study, we aimed to evaluate the potential protective effect of EVO against lipopolysaccharide- (LPS-) induced AKI and cytotoxicity.

LPS-resulted pathological injuries were significantly ameliorated by the administration of EVO.

EVO reduced the levels of blood urea nitrogen (BUN) and creatinine in LPS-treated rats.

EVO also inhibited LPS-induced reduction of cell viability in NRK-52E cells.

LPS-resulting increase of TNFα and IL-1β in both serum and kidney of rats and NRK-52E cells was inhibited by EVO.

LPS-induced increase of P65 NF-κB expression was markedly inhibited by EVO.

EVO-induced reduction of TNFα and IL-1β expression in LPS-treated cells was blocked by overexpression of P65 NF-κB.

Moreover, the increase of cell viability in LPS-treated cells induced by EVO was remarkably suppressed by overexpression of P65 NF-κB.

LPS-resulting increase of reactive oxygen species (ROS) production was suppressed by EVO.

H2O2 suppressed EVO-induced decrease of P65 NF-κB expression and increase of cell viability in LPS-treated NRK-52E cells.

Moreover, the antioxidant NAC significantly promoted EVO-induced decrease of P65 NF-κB expression and increase of cell viability in LPS-treated NRK-52E cells.

In conclusion, EVO had crucial protective effects against LPS-induced AKI and cytotoxicity through the antioxidant activities and thus the inhibition of inflammation.

Our data highlight EVO as a potential candidate for the development of new strategies for the treatment of AKI.