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-α, NOX4, p22phox and NFκB 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, TNFα, NOX4, p22 phox, and NFκB 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).

Nicotinic acetylcholine receptor-mediated effects of varenicline on LPS-elevated prostaglandin and cyclooxygenase levels in RAW 264.7 macrophages

“…Moreover, α7nAChR expression ACh levels, and choline acetyltransferase activity also decreased ( Han et al, 2018 ). We previously demonstrated the therapeutic efficacy of CAP-inducing agents, choline and CDP-choline, in mitigating LPS-induced elevations in ROS, TNFα, and NF-κB levels ( Baris et al, 2023b ). Studies performed on the effects of a 3-month smoking cessation program using varenicline on vascular function and oxidative stress markers showed that after 3 months, participants have decreased levels of carbon monoxide (CO), MDA, protein carbonyls (PC), and augmentation index (Aix), indicating reduced arterial stiffness and oxidative stress.…”

Metabolomics analysis reveals amelioration effects of yellowhorn tea extract on hyperlipidemia, inflammation, and oxidative stress in high-fat diet-fed mice

“…Twenty-one metabolites in the YT extract-treated groups were significantly changed compared with those in the HFD group; the altered metabolite pathways included glycerol phospholipid metabolism, vitamin B6 metabolism, and nicotinate and nicotinamide metabolism, which supported the anti-obesity and lipid-lowering effect of YT extract. Metabolites such as citicholine, acetylcholine, pyridoxine, and NAD have been well reported on the regulation of obesity, dyslipidemia, infection, and oxidative stress ( 50 – 53 ). In the present study, correlation analysis between significantly changed metabolites and metabolic syndrome-related indices further demonstrated that YT extract administration was positively associated with weight loss, alleviation of inflammatory and oxidative stress, and lower hyperlipidemia.…”