Betulin attenuates kidney injury in septic rats through inhibiting TLR4/NF-κB signaling pathway

Aims: This study aims to evaluate the renoprotective effect of betulin and the possible mechanisms in septic rats. Methods: In the animal study, rats underwent cecal ligation and puncture (CLP) were used as septic models. Betulin 4 mg/kg or 8 mg/kg was administrated intraperitoneally immediately after the model establishment. In the cell study, lipopolysaccharide (LPS) stimulated rat HBZY-1 mesangial cells were used. Cells were pretreated with betulin before the LPS stimulation. Histological change of kidney was examined using periodic acid-schiff staining. Serum creatinine and blood urea nitrogen were detected using biochemical assay kits, and proinflammatory factors in kidney and culture medium were detected using ELISA kits. Immunohistochemistry analysis was used to measure F4/80, HMGB-1 and TLR4 expression in renal tissue of rats. mRNA and protein expressions of HMGB-1, TLR4, I kappa B alpha, p65 and p-p65 were measured using Real-time PCR and Western blot, respectively. Nuclear factor kappa-B (NF-kappa B) nuclear translocation was observed using immunofluorescence staining. Key findings: Results showed that betulin attenuated CLP-induced renal damage, reduced levels of serum creatinine and blood urea nitrogen, and decreased the proinflammatory cytokines secretion in the kidney of septic rats and culture medium of LPS-stimulated cells. Betulin could also downregulated HMGB-1 and TLR4 mRNA and protein expression in the kidney of septic rats, as well as inhibited NF-kappa B signal activation. Significance: Our finding suggests that betulin attenuates kidney injury in septic rats through anti-inflammation and TLR4/NF-kappa B signaling inhibition. (C) 2015 Elsevier Inc. All rights reserved.