Abstract

The current study aimed in evaluating the efficacy of quercetin on sepsis-related acute kidney injury and explores its potential mechanisms to provide theoretical support for treatment. A total of forty mice were allocated into four groups; mock, lipopolysaccharide and two quercetin dosage groups (low and high doses; 25 mg/kg and 50 mg/kg, respectively). Kidney tissue morphology was assessed. Serum levels of the kidney function markers creatinine and blood urea nitrogen, as well as inflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6, were measured. A septic injury model was established in human kidney-2 cells using lipopolysaccharide induction, and iron content in human kidney-2 cells and mouse kidney tissues was measured. Reverse transcription-polymerase chain reaction was used to assess the expression levels of ferroptosis-related genes. Spectrophotometry measured malondialdehyde and glutathione levels in human kidney-2 cells and tissues of kidneys in mouse. Enzyme-linked immunosorbent assay was used to quantify nuclear factor erythroid 2-related factor 2 and glutathione peroxidase 4 protein levels. Quercetin intervention 25/50 mg/kg significantly improved the morphology of mouse kidney tissues and decreased serum levels of inflammatory cytokines, and kidney function markers creatinine and blood urea nitrogen, showing a dose-dependent effect. Quercetin significantly reduced the content of ferrous ions and the expression of cyclooxygenase-2 and acyl-coenzyme A synthetase long chain family member 4. The expression levels of nuclear factor erythroid 2-related factor 2 and glutathione peroxidase 4 induced by lipopolysaccharide were significantly downregulated (p<0.001). Quercetin can alleviate sepsis-related acute kidney injury with its mechanism likely involving the activation of the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 pathway.