作者: Baumann, Anja ; Kromm, Franziska ; Yergaliyev, Timur ; Camarinha-Silva, Amélia ; Brandt, Annette ; Bergheim, Ina ; Kopp, Florian ; Scholda, Julia ; Sánchez, Victor

BACKGROUNDChronic alcohol intake is associated with alterations of choline metabolism in various tissues. Here, we assessed if an oral choline supplementation attenuated the development of alcohol-related liver disease (ALD) in mice.METHODSFemale C57BL/6 J mice (n = 8/group) were either pair-fed a liquid control diet, or a Lieber DeCarli liquid diet (5% ethanol) ± 2.7 g choline/kg diet for 29 days. Liver damage, markers of intestinal permeability and intestinal microbiota composition were determined. Moreover, the effects of choline on ethanol-induced intestinal permeability were assessed in an ex vivo model.RESULTSALD development as determined by liver histology and assessing markers of inflammation (e.g., nitric oxide, interleukin 6 and 4-hydroxynonenal protein adducts) was attenuated by the supplementation of choline. Intestinal permeability in small intestine being significantly higher in ethanol-fed mice was at the level of controls in ethanol-fed mice receiving choline. In contrast, no effects of the choline supplementation were found on intestinal microbiota composition. Choline also significantly attenuated the ethanol-induced intestinal barrier dysfunction in small intestinal tissue ex vivo, an effect almost entirely abolished by the choline oxidase inhibitor dimbunol.CONCLUSIONOur results suggest that an oral choline supplementation attenuates the development of ALD in mice and is related to a protection from intestinal barrier dysfunction.

2024-08-26·Bioscience, Biotechnology, and Biochemistry

Regulatory effects of antioxidants on indoxyl sulfate-enhanced intracellular oxidation and impaired phagocytic activity in differentiated U937 human macrophage cells

Article

作者: Suiko, Masahito ; Ikeda, Tomohiro ; Sakakibara, Yoichi ; Ono, Masateru ; Nishikawa, Hirotaka ; Yasuda, Shin ; Hirano, Masashi ; Iwamoto, Wakana ; Kurogi, Katsuhisa ; Kinoshita, Hideki

ABSTRACTIndoxyl sulfate (IS), a uremic toxin, is a physiologically active sulfated metabolite, specifically in kidney failure patients. Our previous studies have shown that IS downregulates phagocytic immune function in a differentiated HL-60 human macrophage cell model. However, it remains unclear whether IS exerts similar effects on macrophage function in other cell types or in lipopolysaccharide (LPS)-sensitive immune cell models. Therefore, this study aimed to investigate the effects of IS on intracellular oxidation levels and phagocytic activity in a differentiated U937 human macrophage cell model, both in the absence and presence of LPS. Our results demonstrated that IS significantly increases intracellular oxidation levels and decreases phagocytic activity, particularly in cells activated by LPS. Furthermore, we found that 2-acetylphenothiazine, an NADH oxidase inhibitor, attenuates the effects of IS in LPS-activated macrophage cells. Representative antioxidants, trolox, α-tocopherol, and ascorbic acid, significantly mitigated the effects of IS on the macrophages responding to LPS.

2024-05-01·NeuroToxicology

Agmatine mitigates behavioral abnormalities and neurochemical dysregulation associated with 3-Nitropropionic acid-induced Huntington's disease in rats

Article

作者: Umekar, Milind ; Mishra, Kartikey ; Sammeta, Shivkumar ; Taksande, Brijesh ; Kotagale, Nandkishor ; Katariya, Raj

Huntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties. The present study was designed to examine the influence of agmatine on the behavioral, biochemical, and molecular aspects of HD in an animal model. A mitochondrial toxin, 3-nitro propionic acid (3-NP), was used to induce HD phenotype and similar symptoms such as motor incoordination, memory impairment, neuro-inflammation, and depressive-like behavior in rats. Rats were pre-treated with 3-NP (10 mg/kg, i.p.) on days 1, 3, 5, 7, and 9 and then continued on agmatine treatment (5 - 20 µg/rat, i.c.v.) from day-8 to day-27 of the treatment protocol. 3-NP-induced cognitive impairment was associated with declined in agmatine levels within prefrontal cortex, striatum, and hippocampus. Further, the 3-NP-treated rats showed an increase in IL-6 and TNF-α and a reduction in BDNF immunocontent within these brain areas. Agmatine treatment not only improved the 3-NP-induced motor incoordination, depression-like behavior, rota-rod performance, and learning and memory impairment but also normalized the GABA/glutamate, BDNF, IL-6, and TNF-α levels in discrete brain areas. Similarly, various agmatine modulators, which increase the endogenous agmatine levels in the brain, such as L-arginine (biosynthetic precursor), aminoguanidine (diamine oxidase inhibitor), and arcaine (agmatinase inhibitor) also demonstrated similar effects exhibiting the importance of endogenous agmatinergic pathway in the pathogenesis of 3-NP-induced HD like symptoms. The present study proposed the possible role of agmatine in the pathogenesis and treatment of HD associated motor incoordination, and psychiatric and cognitive complications.

100 项与 C9-4 相关的药物交易

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