Vitexin Alleviates Lipopolysaccharide-Induced Acute Kidney Injury via Triggering AMPK/FOXO3a Signaling Pathway in Newborn Rats

The purpose was to investigate the effect and the mechanism of vitexin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Newborn rats were randomly divided into 6 groups (n = 6: control, LPS, vitexin (2, 5, and 10 mg/kg) and A-769662 (10 mg/kg). AKI rats were intraperitoneally injected with 4 mg/kg LPS. Vitexin (2, 5, and 10 mg/kg) was administrated in LPS-treated rats. A-769662 (10 mg/kg) and dorsomorphin (Dop, 0.2 mg/kg) were used to investigate the mechanism of vitexin on LPS-induced AKI. Histological changes in kidney tissues, serum creatinine and blood urea nitrogen (BUN) were assessed after 24 h LPS challenge. Western blotting analysis was performed to detect levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), adenosine monophosphate-activated protein kinase (AMPK) and phospho-AMPK (p-AMPK). Forkhead box 03a (FOXO3a) level in cytoplasm and nucleus were measured. After stimulation with LPS for 24 h, levels of serum creatinine, BUN, KIM-1 and NGAL were significantly increased. Vacuoles, dilation and degeneration were observed in kidney tissues. Decreased p-AMPK to AMPK ratio, and higher protein level of FOXO3a in cytoplasm, as well as downregulated FOXO3a level were observed in nucleus after LPS stimulation. Vitexin significantly decreased levels of serum creatinine and BUN, KIM-1 and NGAL. LPS-induced renal injuries in kidney tissues were remarkably alleviated by vitexin. In addition, vitexin (10 mg/kg) activated AMPK/FOXO3a signaling pathway through elevating p-AMPK to AMPK ratio and protein level of FOXO3a in nucleus, whereas downregulating FOXO3a level in cytoplasm. However, the benefit of vitexin was clearly prevented by Dop. Vitexin alleviated LPS-induced AKI through activating AMPK/FOXO3a pathway.