Choline and citicoline ameliorate oxidative stress in acute kidney injury in rats

Abstract

OBJECTIVES: The purpose of this study is to investigate the effects of cholinergic anti-infl ammatory pathway (CAP)-activating drugs, choline and citicoline (Cytidinediphosphate-choline, CDP-choline), on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) parameters and the contribution of NADPH Oxidase4 (NOX4) p22phox. BACKGROUND: Endotoxemia induces a systemic infl ammatory response characterized by the production of pro-infl ammatory mediators and reactive oxygen species (ROS), which eventually develops acute kidney injury (AKI). NADPH Oxidase4 (NOX4) p22phox pathway contributes to the development of endotoxemiainduced AKI. Infl ammatory response can be controlled by CAP. METHODS: Expressions levels of KIM-1, TNF-?, NOX4, p22phox and NF?B in the kidney tissues of rats were analyzed via RT-PCR in experimental groups; 1. Control, 2. LPS (10 mg/kg) + saline, 3. LPS + CDPcholine (375 mg/kg) and 4. LPS + choline (90 mg/kg). Choline and ROS levels in kidney tissues were also measured by a spectrofl uorometric assay. RESULTS: LPS-induced elevations of ROS levels were decreased by CDP-choline or choline administration (p < 0.001). LPS-elevated KIM-1, TNF?, NOX4, p22 phox, and NF?B expressions were signifi cantly decreased by choline or CDP-choline treatments (p < 0.001). CONCLUSION: Decreased ROS production in kidney tissues in treatment groups suggests that choline or CDP-choline may have therapeutic potential in endotoxemia-associated AKI via downregulating NOX4 and p22phox expressions (Tab. 1, Fig. 5, Ref. 45). Text in PDF www.elis.sk © 2022,Kragujevac Journal of Mathematics. All Rights Reserved.