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05 January 2019 : Laboratory Research  

β-Casomorphin-7 Ameliorates Sepsis-Induced Acute Kidney Injury by Targeting NF-κB Pathway

ZhiJie Zhang1ABCE, Huatang Zhao2BCE, DongJian Ge1BCF, Shanshan Wang3DFG, Bin Qi1ACFG*

DOI: 10.12659/MSM.912730

Med Sci Monit 2019; 25:121-127

Abstract

BACKGROUND: The aim of this study was to investigate the protective effect of β-casomorphin-7 (β-CM-7) and its possible mechanisms on acute kidney injury (AKI).

MATERIAL AND METHODS: Rats were randomly divided into a sham group, a cecal ligation and puncture (CLP) group, and a CLP+β-CM-7 group. Kidney index, kidney function, and histopathology changes were assessed. The expression of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and p-IκBα in kidney tissues were detected by Western blotting. Inflammatory and oxidative stress factors were detected by ELISA kits.

RESULTS: The results showed that treatment with β-CM-7 reduced the levels of creatinine (Cre), blood urea nitrogen (BUN), NGAL, and Kim-1 induced by CLP, weakening the pathological damage. In the CLP + β-CM-7 group, the tumor necrosis factor-α (TNF-α) level and the DNA-binding activity of NF-κB p65 were significantly reduced and the interleukin-10 (IL-10) level was significantly increased compared with the CLP group. β-CM-7 decreased the expression of p-IκBα/IκBα. In addition, β-CM-7 increased the activity of superoxide dismutase (SOD) and decreased the level of malondialdehyde (MDA) in kidney tissue.

CONCLUSIONS: β-CM-7 attenuated sepsis-induced AKI through reducing inflammation and oxidative stress and by inhibition of nuclear factor (NF)‑κB activities. This study provides a new therapeutic agent for attenuating sepsis-induced kidney injury.

Keywords: Acute Kidney Injury, Blood Urea Nitrogen, Cecum, Cell Adhesion Molecules, Creatinine, Endorphins, Kidney, Ligation, Lipocalin-2, Malondialdehyde, NF-KappaB Inhibitor alpha, Peptide Fragments, Sepsis

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750