Asiatic acid alleviates LPS-induced acute kidney injury in broilers by inhibiting oxidative stress and ferroptosis via activation of the Nrf2 pathway

Asiatic acid (AA), a triterpenoid compound isolated from Centella asiatica, has anti-inflammatory, antioxidant and anticancer biological characteristics. To explore the effect of AA on LPS-induced acute kidney injury (AKI) in broilers, a total of 60 one-day-old broilers were randomly divided into 6 groups, including the normal group, AKI model group, AKI + AA 15 mg/kg group, AKI + AA 30 mg/kg group, AKI + AA 60 mg/kg group and normal + AA 60 mg/kg group. Hematoxylin-eosin staining was used to observe the histopathology in kidney tissue, and the mRNA and protein expressions related to oxidative stress and ferroptosis were tested by qPCR and western blotting respectively. AA mitigated vacuolar degeneration and enlarged glomerular space caused by LPS in kidney tissue. Additionally, AA significantly increased the mRNA levels of Nrf2, HO-1, NQO1, GCLC, GCLM, GPX4, SLC7A11 and FTH1, and decreased the mRNA levels of Keap1 and PTGS2 in LPS-induced AKI. Likewise, AA significantly upregulated the protein expressions of Nrf2, HO-1, NQO1, GPX4, SLC7A11 and FTH1, and downregulated the protein expressions of Keap1 and PTGS2 in LPS-induced AKI. These results suggested that AA alleviated LPS-induced AKI by inhibiting oxidative stress and ferroptosis through targeting regulation of the Nrf2 pathway in broilers. LPS caused oxidative stress and ferroptosis in the kidneys of broilers. Interestingly, Asiatic acid (AA) attenuated acute kidney injury (AKI) induced by LPS. AA attenuated LPS-induced oxidative stress by promoting Nrf2 translocation into the nucleus and activating its downstream genes. In addition, AA alleviated LPS-induced ferroptosis by regulation of the SLC7A11/GPX4 axis. In brief, AA alleviated LPS-induced AKI in broilers by inhibiting oxidative stress and ferroptosis via activating the Nrf2 pathway. [Display omitted] •LPS induces oxidative stress and ferroptosis in broiler kidneys.•Asiatic acid alleviates oxidative stress by activating Nrf2 expression in AKI.•Asiatic acid suppresses ferroptosis in LPS-induced AKI via the SLC7A11/GPX4 axis.•Asiatic acid is a promising therapeutic candidate for AKI caused by LPS.