Salete-Granado Daniel, Carbonell Cristina, Puertas-Miranda David, Vega-Rodríguez Víctor-José, García-Macia Marina, Herrero Ana Belén, Marcos Miguel
Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.
Hospital Universitario de Salamanca, 37007 Salamanca, Spain.
Antioxidants (Basel). 2023 Jul 14;12(7):1425. doi: 10.3390/antiox12071425.
Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic liver disease (ALD). Autophagy is a regulated dynamic process that sequesters damaged and excess cytoplasmic organelles for lysosomal degradation and may counteract the harmful effects of ROS-induced oxidative stress. These effects include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, inflammation, and iron overload. In liver diseases, particularly ALD, macroautophagy has been implicated as a protective mechanism in hepatocytes, although it does not appear to play the same role in stellate cells. Beyond the liver, autophagy may also mitigate the harmful effects of alcohol on other organs, thereby providing an additional layer of protection against ALD. This protective potential is further supported by studies showing that drugs that interact with autophagy, such as rapamycin, can prevent ALD development in animal models. This systematic review presents a comprehensive analysis of the literature, focusing on the role of autophagy in oxidative stress regulation, its involvement in organ-organ crosstalk relevant to ALD, and the potential of autophagy-targeting therapeutic strategies.
乙醇的摄入通过其代谢产物产生活性氧（ROS）引发氧化应激。这一过程会导致脂肪变性和肝脏炎症，而这对于酒精性肝病（ALD）的发展至关重要。自噬是一个受调控的动态过程，它会隔离受损和多余的细胞质细胞器以便溶酶体进行降解，并且可能抵消ROS诱导的氧化应激的有害影响。这些影响包括肝毒性、线粒体损伤、脂肪变性、内质网应激、炎症和铁过载。在肝脏疾病中，尤其是ALD，尽管自噬在星状细胞中似乎没有发挥相同的作用，但巨自噬已被认为是肝细胞中的一种保护机制。除肝脏外，自噬还可能减轻酒精对其他器官的有害影响，从而为ALD提供额外一层保护。与自噬相互作用的药物（如雷帕霉素）能够在动物模型中预防ALD发展的研究进一步支持了这种保护潜力。本系统综述对文献进行了全面分析，重点关注自噬在氧化应激调节中的作用、其在与ALD相关的器官-器官串扰中的参与情况以及靶向自噬的治疗策略的潜力。
