Kromm Franziska, Baumann Anja, Sánchez Victor, Brandt Annette, Staltner Raphaela, Bergheim Ina
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Josef-Holaubek-Platz 2, UZA II, Vienna, A-1090, Austria.
J Mol Med (Berl). 2025 Aug 7. doi: 10.1007/s00109-025-02583-4.
Studies suggest that supplementing melatonin in pharmacological doses may attenuate the development of liver diseases including alcohol-related liver diseases (ALD) in model organisms. If melatonin at "physiological" doses achievable through the intake of foods and beverages affects the development of liver diseases, it has not yet been clarified; therefore, we assessed whether supplementing "dietary doses" of melatonin affects the development of ALD in mice. Female 6-8-week-old C57BL/6J mice were either pair-fed a liquid alcohol-enriched Lieber DeCarli diet or a control diet ± melatonin (50 ng/kg BW/day) for 6 weeks. Markers of liver damage and intestinal barrier function were assessed. Moreover, the effects of melatonin on intestinal barrier function were assessed in an ex vivo model. Supplementing melatonin significantly attenuated the development of ALD being related to lower interleukin-6 protein, NOx, and 4-hydroxynonenal protein adduct levels in liver tissue. Impairments of intestinal barrier function in small intestine in ethanol-fed mice were significantly attenuated in ethanol-fed mice treated with melatonin being associated with lower NOx and higher phosphorylation levels of AMPK. In summary, our results suggest that an oral supplementation of "dietary" doses of melatonin may dampen the development of ALD in mice. KEY MESSAGES: Supplementation of "dietary" doses of melatonin dampens the development of ALD. Melatonin attenuates alcohol-induced small intestinal barrier dysfunction. Protective role of melatonin is related to alterations of AMPK activity.
研究表明，以药理剂量补充褪黑素可能会减轻模型生物中包括酒精性肝病（ALD）在内的肝脏疾病的发展。通过摄入食物和饮料所能达到的“生理”剂量的褪黑素是否会影响肝脏疾病的发展，目前尚未明确；因此，我们评估了补充“膳食剂量”的褪黑素是否会影响小鼠ALD的发展。6至8周龄的雌性C57BL/6J小鼠分别成对喂食富含酒精的液体Lieber DeCarli饮食或对照饮食±褪黑素（50 ng/kg体重/天），持续6周。评估肝脏损伤和肠道屏障功能的标志物。此外，在体外模型中评估褪黑素对肠道屏障功能的影响。补充褪黑素显著减轻了ALD的发展，这与肝脏组织中白细胞介素-6蛋白、NOx和4-羟基壬烯醛蛋白加合物水平降低有关。在喂食乙醇的小鼠中，用褪黑素处理后，小肠中肠道屏障功能的损伤显著减轻，这与较低的NOx和较高的AMPK磷酸化水平有关。总之，我们的结果表明，口服补充“膳食”剂量的褪黑素可能会抑制小鼠ALD的发展。关键信息：补充“膳食”剂量的褪黑素可抑制ALD的发展。褪黑素可减轻酒精诱导的小肠屏障功能障碍。褪黑素的保护作用与AMPK活性的改变有关。
