Effects of yohimbine against lipopolysaccharide-induced acute kidney injury in rats

[Speaker] Takaomi Shimokawa:1
[Co-author] Kozo Yoneda:1
1:Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Japan

Sepsis-induced acute kidney injury (AKI) is frequently observed in the intensive care unit. We previously revealed that yohimbine, α2-adrenoceptor antagonist, has protective effect against renal ischemia/reperfusion injury-induced AKI in rats. The present study aimed to investigate the renoprotective effect of yohimbine against lipopolysaccharide (LPS) - induced AKI in rats. Male Sprague Dawley rats were randomly divided into following groups: Sham-operated group, LPS (10 mg/kg, i.p.), LPS + yohimbine (0.1 or 0.5 mg/kg, i.p.). LPS group were aggravated kidney functional parameters of blood urea nitrogen (BUN), plasma creatinine (Pcr). In addition, kidney injury molecule-1 and various cytokine expression such as TNF-α, MCP-1 and IL-6 were increased by LPS. The treatment with yohimbine clearly ameliorated damaged kidney function due to LPS. Moreover, yohimbine suppressed dose-dependently cytokine mRNA expression enhanced by LPS. However, IL-10 which is anti-inflammatory cytokine mRNA levels were augmented by yohimbine. NF-κB nuclear translocation in kidney incresed 1 hr after injection of LPS in rats, yohimbine could decreased nuclear entry of NF-κB. In addition, phosphorylation of ERK and CREB were enhanced by yohimbine. These results suggest that yohimbine can prevent LPS-induced sepsis associated with kidney injury by suppressing the inflammatory cytokine expression and enhancement of IL-10 expression via ERK/CREB phosphorylation.
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