Shen Yingyan, Huang Hanmei, Wang Yunhong, Yang Rongping, Ke Xiumei
Key Laboratory Breeding Base of Systematic Research and Utilization on Chinese Meterial, Medical Resources Co-founded by Sichuan Province and Ministry of Science and Technology, Chengdu University of Traditional Chinese Medicine, Chendu, China.
Chongqing Key Laboratory of Chinese Medicine New Drug Screening, Southwest University, Chongqing, China.
J Trace Elem Med Biol. 2022 Dec;74:127048. doi: 10.1016/j.jtemb.2022.127048. Epub 2022 Jul 29.
Oxidative damage induced by ethanol and its metabolites is one of the factors that fuels the development of alcoholic liver disease (ALD). Selenium (Se) is an effective cofactor for glutathione peroxidase (GPx), and has antioxidant effects that improve ALD. In patients with ALD, ethanol-induced oxidative damage inhibits the synthesis of related Se-containing proteins such as: selenoprotein P (Sepp1), albumin (ALB), and GPx in the liver, thus decreasing the overall Se level in patients. Both Se deficiency and excess can affect the expression of GPx, resulting in damage to the antioxidant defense system. This damage enhances oxidative stress by increasing the levels of reactive oxygen species (ROS) in the body, which aggravates the inflammatory response, lipid metabolism disorder, and lipid peroxidation and worsens ALD symptoms. A cascade of oxidative damages caused by ALD will deplete selenium deposition in the body, stimulate the expression of Gpx1, Sepp1, and Gpx4, and thus mobilize systemic selenoproteins, which can restore GPx activity in the hepatocytes of ALD patients, reduce the levels of reactive oxygen species and alleviate oxidative stress, the inflammatory response, lipid metabolism disorder, and lipid peroxidation, thus helping to mitigate ALD. This review provides a reference for future ALD studies that evaluate the regulation of Se levels and contributes to studies on the potential pathological mechanisms of Se imbalance in ALD.
乙醇及其代谢产物诱导的氧化损伤是导致酒精性肝病（ALD）发展的因素之一。硒（Se）是谷胱甘肽过氧化物酶（GPx）的有效辅因子，具有改善ALD的抗氧化作用。在ALD患者中，乙醇诱导的氧化损伤会抑制肝脏中相关含硒蛋白的合成，如硒蛋白P（Sepp1）、白蛋白（ALB）和GPx，从而降低患者的总体硒水平。硒缺乏和过量都会影响GPx的表达，导致抗氧化防御系统受损。这种损伤会通过增加体内活性氧（ROS）水平来增强氧化应激，进而加剧炎症反应、脂质代谢紊乱和脂质过氧化，使ALD症状恶化。ALD引起的一系列氧化损伤会消耗体内的硒沉积，刺激Gpx1、Sepp1和Gpx4的表达，从而调动全身硒蛋白，这可以恢复ALD患者肝细胞中的GPx活性，降低活性氧水平，减轻氧化应激、炎症反应、脂质代谢紊乱和脂质过氧化，从而有助于减轻ALD。本综述为未来评估硒水平调节的ALD研究提供了参考，并有助于研究ALD中硒失衡的潜在病理机制。
