β-hydroxybutyrate ameliorates sepsis-induced acute kidney injury

Abstract

Background: Sepsis is a major cause of acute kidney injury (AKI). Recent studies have demonstrated that β-hydroxybutyrate (β-HB) alleviates renal ischemia-reperfusion injury and cisplatin-induced renal injury in murine models. This study aimed to investigate whether β-HB ameliorates sepsis-induced AKI (SIAKI) in a lipopolysaccharide (LPS)-induced mouse sepsis model.

Methods and results: SIAKI was induced by intraperitoneally injecting LPS to C57BL/6 male mice. β-HB was administrated intraperitoneally before LPS injection. The mice were divided into sham, β-HB, LPS, and β-HB + LPS groups. The histological damage score and serum creatinine level were significantly increased in the LPS group mice, but attenuated in the β-HB + LPS group mice. The expression of phosphorylated nuclear factor-κB tumor necrosis factor-α/interleukin-6 and the number of F4/80-positive macrophages in the β-HB + LPS group mice were lower than those in the LPS group mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells, cleaved caspase-3 expression, and Bax/Bcl-2 ratio in the β-HB + LPS group mice were lower than those in the LPS group mice.

Conclusion: β-HB pre-treatment ameliorates SIAKI by reducing tubular apoptosis and inflammatory responses. Thus, β-HB pre-treatment could be a potential prophylactic strategy against SIAKI.

Keywords: Acute kidney injury; Apoptosis; Inflammation; Sepsis; β-hydroxybutyrate.