Arauz Jonathan, Ramos-Tovar Erika, Muriel Pablo
Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Baja California, Mexicali, Baja California, México.
Departamento de Farmacología, CINVESTAV-IPN. Mexico City, México.
Ann Hepatol. 2016 Mar-Apr;15(2):160-73. doi: 10.5604/16652681.1193701.
Oxidative stress is importantly involved in the pathophysiology of various liver diseases. The redox state participates on the course of the inflammatory, metabolic and proliferative liver diseases. The main sources of the reactive oxygen species (ROS) are represented by the mitochondria and cytochrome P450 enzymes in the hepatocyte, Kupffer cells and neutrophils. Cells are provided with efficient molecular strategies to strictly control the intracellular ROS level and to maintain the balance between oxidant and antioxidant molecules. Hepatocyte's proteins, lipids and DNA are among the cellular structures to be affected primarily by ROS and reactive nitrogen species (RNS). This process disrupts at cellular and molecular level the structure-function relationship on liver cells at different sites. Therefore, further studies on the molecular mechanisms of the oxidative stress pathways on liver diseases are urgently required, because they could explain the pathogenesis of various liver disorders. Moreover, new methods to evaluate oxidative stress like the oxidative markers among hepatocytes offers the potential to diagnose the degree of liver injury and ultimately to assess the response to pharmacological therapies. In this review, we discuss the molecular, metabolic and aging aspects of the oxidative stress, and the methods to evaluate oxidative stress on liver damage.
氧化应激在各种肝脏疾病的病理生理学中起着重要作用。氧化还原状态参与炎症性、代谢性和增殖性肝脏疾病的病程。活性氧(ROS)的主要来源是肝细胞、库普弗细胞和中性粒细胞中的线粒体和细胞色素P450酶。细胞具有有效的分子策略来严格控制细胞内ROS水平,并维持氧化剂和抗氧化剂分子之间的平衡。肝细胞的蛋白质、脂质和DNA是主要受ROS和活性氮(RNS)影响的细胞结构。这一过程在细胞和分子水平上破坏了不同部位肝细胞的结构-功能关系。因此,迫切需要进一步研究肝脏疾病氧化应激途径的分子机制,因为它们可以解释各种肝脏疾病的发病机制。此外,评估氧化应激的新方法,如肝细胞中的氧化标记物,有可能诊断肝损伤程度,并最终评估对药物治疗的反应。在这篇综述中,我们讨论了氧化应激的分子、代谢和衰老方面,以及评估氧化应激对肝损伤的方法。