Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice

作者：Qian Ren, Fan Guo, Sibei Tao, Rongshuang Huang, Liang Ma, Ping Fu · 发表于：Biomedicine & Pharmacotherapy · 年份：2019 · DOI：10.1016/j.biopha.2019.109772 · 被引用次数：422 · 研究领域：Acute Kidney Injury Research、Flavonoids in Medical Research、Natural Compounds in Disease Treatment

BACKGROUND: Sepsis is defined as end-organ dysfunction resulting from the host's inflammatory response to infection. One of the most common sepsis-injured organs is the kidneys, resulting in acute kidney injury (AKI) that contributes to the high morbidity and mortality, especially patients in the intensive care unit. Fisetin, a naturally occurring flavonoid, has been reported to protect against the rat of lipopolysaccharide (LPS)-induced acute lung injury. However, the effect of fisetin on septic AKI remains unknown. PURPOSE: The current study proposed to systematically investigate the renoprotective effects and the underlying mechanisms of fisetin in septic AKI mice. METHODS: The model of septic AKI was established on male C57BL/6 J mice by a single intraperitoneal injection of LPS (10 mg/kg). Fisetin was administrated by gavage at 100 mg/kg for 3 consecutive days before LPS injection and the mice were sacrificed at 16 h after LPS injection. The serum and kidney samples were evaluated for biochemical analysis, histopathological examinations as well as inflammation and apoptosis related gene/protein expression. RESULTS: Pretreatment with fisetin significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in LPS-treated mice. Consistently, LPS induced renal damage as implied by histopathological score and the increased injury markers NGAL and KIM-1, which was attenuated by fisetin. Meanwhile, LPS injection triggered proinflammatory cytokine product...