Abstract
Sepsis-induced acute kidney injury (AKI) is frequently observed in the intensive care unit. We previously revealed that yohimbine, an α2-adrenoceptor antagonist, has protective effects on renal ischemia/reperfusion injury-induced AKI in rats. This study aimed to investigate the renoprotective effect of yohimbine on lipopolysaccharide (LPS)-induced AKI in rats. Male Sprague Dawley rats were randomly divided into the following groups: Sham-operated group, LPS (10 mg/kg, i.p.) and LPS + yohimbine (0.1 or 0.5 mg/kg, i.p.). Kidney functional parameters of blood urea nitrogen (BUN) and plasma creatinine (Pcr) were aggravated in the LPS group. Administration of LPS decreased blood pressure. In addition, kidney injury molecule-1, inducible nitric oxide synthase (iNOS) and expression of various cytokines such as tumour necrosis factor-α, monocyte chemoattractant protein-1, and interleukin (IL)-6 were increased by LPS administration. Yohimbine treatment clearly ameliorated the damaged kidney function and low blood pressure due to LPS. Moreover, yohimbine suppressed cytokine mRNA and iNOS expression enhanced by LPS. However, anti-inflammatory cytokine IL-10 mRNA levels were augmented by yohimbine. Nuclear localization of nuclear factor-kappa B (NF-κB) in the kidney was observed 1 h after injection of LPS in rats. Yohimbine blocked the nuclear localization of NF-κB. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were enhanced with yohimbine. These results suggest that yohimbine can prevent LPS-induced sepsis associated with kidney injury by suppressing inflammatory cytokine and iNOS expression as well as enhancing IL-10 expression via ERK/CREB phosphorylation.