Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney injury in a mouse model by inhibiting oxidative stress and inflammatory responses

摘要

Ursolic acid (UA) as a multiple bioactive native compound has recently been demonstrated to treat sepsis in animal models. However, the beneficial effects of UA in sepsis-induced acute kidney injury (AKI) are not completely understood. In the present study, the effect of UA on sepsis-induced AKI in cecal ligation and puncture (CLP) surgery mice was investigated. Renal histomorphological analysis was performed by hematoxylin and eosin staining. The expression of inflammatory markers in the kidney of septic mice was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that UA administration improved survival in septic mice induced by CLP surgery. The treatment with UA revealed protection against AKI induced by CLP surgery, including the alleviation of glomerular damage and vacuolization in the proximal tubules. In addition, the effects of UA on oxidative stress and inflammation in septic mice were determined. The findings suggested that UA may protect against sepsis-induced AKI by inhibiting reactive oxygen species and inflammatory cytokines, including tumor necrosis factor-, interleukin (IL)-1 and IL-6, in the kidney from septic mice. Finally, UA inhibited CLP-induced activation of nuclear factor-B signaling in the kidney from septic mice. The findings of the present study demonstrated that UA may be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.