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{"title":"Oxidative Stress and Redox Signaling in the Pathophysiology of Liver Diseases.","authors":"Raja Gopal Reddy Mooli, Dhanunjay Mukhi, Sadeesh K Ramakrishnan","doi":"10.1002/cphy.c200021","DOIUrl":null,"url":null,"abstract":"<p><p>The increased production of derivatives of molecular oxygen and nitrogen in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS) lead to molecular damage called oxidative stress. Under normal physiological conditions, the ROS generation is tightly regulated in different cells and cellular compartments. Any disturbance in the balance between the cellular generation of ROS and antioxidant balance leads to oxidative stress. In this article, we discuss the sources of ROS (endogenous and exogenous) and antioxidant mechanisms. We also focus on the pathophysiological significance of oxidative stress in various cell types of the liver. Oxidative stress is implicated in the development and progression of various liver diseases. We narrate the master regulators of ROS-mediated signaling and their contribution to liver diseases. Nonalcoholic fatty liver diseases (NAFLD) are influenced by a \"multiple parallel-hit model\" in which oxidative stress plays a central role. We highlight the recent findings on the role of oxidative stress in the spectrum of NAFLD, including fibrosis and liver cancer. Finally, we provide a brief overview of oxidative stress biomarkers and their therapeutic applications in various liver-related disorders. Overall, the article sheds light on the significance of oxidative stress in the pathophysiology of the liver. © 2022 American Physiological Society. Compr Physiol 12:3167-3192, 2022.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"12 2","pages":"3167-3192"},"PeriodicalIF":4.2000,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074426/pdf/nihms-1880813.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comprehensive Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cphy.c200021","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
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Abstract
The increased production of derivatives of molecular oxygen and nitrogen in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS) lead to molecular damage called oxidative stress. Under normal physiological conditions, the ROS generation is tightly regulated in different cells and cellular compartments. Any disturbance in the balance between the cellular generation of ROS and antioxidant balance leads to oxidative stress. In this article, we discuss the sources of ROS (endogenous and exogenous) and antioxidant mechanisms. We also focus on the pathophysiological significance of oxidative stress in various cell types of the liver. Oxidative stress is implicated in the development and progression of various liver diseases. We narrate the master regulators of ROS-mediated signaling and their contribution to liver diseases. Nonalcoholic fatty liver diseases (NAFLD) are influenced by a "multiple parallel-hit model" in which oxidative stress plays a central role. We highlight the recent findings on the role of oxidative stress in the spectrum of NAFLD, including fibrosis and liver cancer. Finally, we provide a brief overview of oxidative stress biomarkers and their therapeutic applications in various liver-related disorders. Overall, the article sheds light on the significance of oxidative stress in the pathophysiology of the liver. © 2022 American Physiological Society. Compr Physiol 12:3167-3192, 2022.
肝脏疾病病理生理学中的氧化应激和氧化还原信号转导。
分子氧和氮的衍生物以活性氧(ROS)和活性氮(RNS)的形式产生,它们的增加会导致被称为氧化应激的分子损伤。在正常生理条件下,ROS 的生成在不同的细胞和细胞间隙中受到严格调控。细胞产生的 ROS 与抗氧化平衡之间的任何失调都会导致氧化应激。本文将讨论 ROS 的来源(内源性和外源性)和抗氧化机制。我们还重点讨论了氧化应激在肝脏各类细胞中的病理生理意义。氧化应激与各种肝脏疾病的发生和发展有关。我们讲述了 ROS 介导的信号转导的主调节因子及其对肝病的影响。非酒精性脂肪肝(NAFLD)受 "多重平行打击模型 "的影响,其中氧化应激起着核心作用。我们重点介绍了氧化应激在非酒精性脂肪肝(包括肝纤维化和肝癌)中的作用的最新发现。最后,我们简要概述了氧化应激生物标志物及其在各种肝脏相关疾病中的治疗应用。总之,文章揭示了氧化应激在肝脏病理生理学中的重要意义。© 2022 美国生理学会。Compr Physiol 12:3167-3192, 2022.
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