Department of Internal Medicine, University of Turin, Turin, Italy.
Antioxid Redox Signal. 2011 Sep 1;15(5):1325-65. doi: 10.1089/ars.2009.3058. Epub 2011 Apr 20.
Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease in the world. It encompasses a histological spectrum, ranging from simple, nonprogressive steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. While liver-related complications are confined to NASH, emerging evidence suggests both simple steatosis and NASH predispose to type 2 diabetes and cardiovascular disease. The pathogenesis of NAFLD is currently unknown, but accumulating data suggest that oxidative stress and altered redox balance play a crucial role in the pathogenesis of steatosis, steatohepatitis, and fibrosis. We will examine intracellular mechanisms, including mitochondrial dysfunction and impaired oxidative free fatty acid metabolism, leading to reactive oxygen species generation; additionally, the potential pathogenetic role of extracellular sources of reactive oxygen species in NAFLD, including increased myeloperoxidase activity and oxidized low density lipoprotein accumulation, will be reviewed. We will discuss how these mechanisms converge to determine the whole pathophysiological spectrum of NAFLD, including hepatocyte triglyceride accumulation, hepatocyte apoptosis, hepatic inflammation, hepatic stellate cell activation, and fibrogenesis. Finally, available animal and human data on treatment opportunities with older and newer antioxidant will be presented.
非酒精性脂肪性肝病（NAFLD）是目前世界上最常见的肝脏疾病。它包含一个组织学谱，从简单的、非进展性脂肪变性到非酒精性脂肪性肝炎（NASH），后者可能进展为肝硬化和肝细胞癌。虽然与肝脏相关的并发症仅限于 NASH，但新出现的证据表明，单纯性脂肪变性和 NASH 可导致 2 型糖尿病和心血管疾病。NAFLD 的发病机制目前尚不清楚，但越来越多的证据表明，氧化应激和氧化还原平衡的改变在脂肪变性、脂肪性肝炎和纤维化的发病机制中起着关键作用。我们将检查细胞内机制，包括线粒体功能障碍和氧化游离脂肪酸代谢受损，导致活性氧的产生；此外，还将回顾细胞外活性氧源在 NAFLD 中的潜在发病作用，包括髓过氧化物酶活性增加和氧化低密度脂蛋白积累。我们将讨论这些机制如何汇聚在一起，决定 NAFLD 的整个病理生理谱，包括肝细胞甘油三酯积累、肝细胞凋亡、肝炎症、肝星状细胞激活和纤维化。最后，将介绍关于使用旧的和新的抗氧化剂治疗机会的可用动物和人类数据。
