Afzelin Alleviates Sepsis Induced Kidney Injury Through Nrf2/Ho-1 and p38 MAPK Signaling Pathways

Sepsis induces various complications throughout the whole body, including acute kidney injury. Afzelin functions as a bioactive flavanol glycoside to exert antioxidant and anti-inflammatory activities against several disease conditions. The role of afzelin in sepsis associated acute kidney injury was investigated in this study. To this end, sepsis was induced in mice through cecal ligation and puncture that presented itself with severe kidney injury, viz. compressed and narrowed hepatic sinus, irregularly arranged hepatic cord, and severe hepatocyte swelling. Also, serum levels of creatinine, blood urea nitrogen, and cystatin C were elevated in the septic mice. Administration of afzelin to septic mice not only corrected the morphological and biochemical changes and suppress the renal apoptosis, but it also decreased the serum levels of oxidants (malondialdehyde and reactive oxygen species), increased the levels of antioxidants (glutathione and superoxide dismutase), and suppressed rise in proinflammatory cytokines. Lastly, afzelin also reversed upregulation of phosphorylated p38 and NLR family (pyrin domain containing 3) proteins, downregulation of nuclear factor erythropoietin-2-related factor 2 and heme oxygenase-1 in septic mice. In conclusion, afzelin exerts antiapoptotic, antioxidant, and anti-inflammatory effects against sepsis induced acute kidney injury through activation of Nrf2/HO-1 and inactivation of p38 MAPK signaling.