Abstract
Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factoralpha (TNFα) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of the Gramnegative bacterial outer membrane). Immune cells use ROS in order to support their functions and need adequate levels of antioxidant defenses to avoid harmful effects of an excessive ROS production. In addition, nitric oxide (NO) is thought to play a key role in the pathogenesis of sepsis and in the development of multiple organ failure. This article discusses the toxic effects of endotoxin, paying particular attention to cardiovascular damage. It continues by analysing the mechanism by which endotoxin is recognized by specific cells of the immune system, and the pathway leading to nuclear factor-kB (NF-kB) activation and pro-inflammatory gene transcription. In relation to this process, this review focuses on the involvement of reactive oxygen and nitrogen species. Finally, the protective role of antioxidants against homeostatic disturbances such as those caused by endotoxin toxicity, their potential clinical use and the effects on the redox state of the immune cells is discussed.
Keywords: endotoxin, reactive oxygen species, nitric oxide, antioxidant, septic shock, cardiovascular dysfunction, mitochondria
Current Pharmaceutical Design
Title: Role of Free Radicals in Sepsis: Antioxidant Therapy
Volume: 11 Issue: 24
Author(s): V. M. Victor, M. Rocha, J. V. Esplugues and M. De la Fuente
Affiliation:
Keywords: endotoxin, reactive oxygen species, nitric oxide, antioxidant, septic shock, cardiovascular dysfunction, mitochondria
Abstract: Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factoralpha (TNFα) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of the Gramnegative bacterial outer membrane). Immune cells use ROS in order to support their functions and need adequate levels of antioxidant defenses to avoid harmful effects of an excessive ROS production. In addition, nitric oxide (NO) is thought to play a key role in the pathogenesis of sepsis and in the development of multiple organ failure. This article discusses the toxic effects of endotoxin, paying particular attention to cardiovascular damage. It continues by analysing the mechanism by which endotoxin is recognized by specific cells of the immune system, and the pathway leading to nuclear factor-kB (NF-kB) activation and pro-inflammatory gene transcription. In relation to this process, this review focuses on the involvement of reactive oxygen and nitrogen species. Finally, the protective role of antioxidants against homeostatic disturbances such as those caused by endotoxin toxicity, their potential clinical use and the effects on the redox state of the immune cells is discussed.
Export Options
About this article
Cite this article as:
Victor M. V., Rocha M., Esplugues V. J. and Fuente De la M., Role of Free Radicals in Sepsis: Antioxidant Therapy, Current Pharmaceutical Design 2005; 11 (24) . https://dx.doi.org/10.2174/1381612054864894
DOI https://dx.doi.org/10.2174/1381612054864894 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Polyphenols and Neuroprotection against Ischemia and Neurodegeneration
Mini-Reviews in Medicinal Chemistry Nitric Oxide and its Antithrombotic Action in the Cardiovascular System
Current Drug Targets - Cardiovascular & Hematological Disorders The Fetal Cardiac Function
Current Cardiology Reviews Novel Lipid and Polymeric Materials as Delivery Systems for Nucleic Acid Based Drugs
Current Drug Metabolism Therapeutic Modulation of Coagulation and Fibrinolysis in Acute Lung Injury and the Acute Respiratory Distress Syndrome
Current Pharmaceutical Biotechnology The Future of Induced Pluripotent Stem Cells for Cardiac Therapy and Drug Development
Current Pharmaceutical Design Allosteric Enhancers of A1 Adenosine Receptors: State of the Art and New Horizons for Drug Development
Current Medicinal Chemistry Treating Arterial Stiffness in Young and Elderly Patients with the Metabolic Syndrome
Current Pharmaceutical Design Endothelial Dysfunction, Impaired Endogenous Platelet Inhibition and Platelet Activation in Diabetes and Atherosclerosis
Current Vascular Pharmacology Mitochondrial Oxidative Stress and Heart Failure ∼Novel Pathophysiological Insight and Treatment Strategies∼
Current Cardiology Reviews Pharmacology of Adenosine A2A Receptors and Therapeutic Applications
Current Topics in Medicinal Chemistry New Horizons in Diabetes Therapy: The Angiogenesis Paradox in Diabetes: Description of the Problem and Presentation of a Unifying Hypothesis
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Stem Cell Therapy for the Treatment of Acute Myocardial Infarction and Chronic Ischemic Heart Disease
Current Pharmaceutical Biotechnology Reactions of Water-Soluble Alkylperoxyl Radicals and Superoxide with DNA, Lipoproteins and Phospholipid Vesicles:The Role Played by Electrostatic Forces
Current Medicinal Chemistry Elevated Serum Levels of Ischemia Modified Albumin and Malondialdehyde are Related to Atherogenic Index of Plasma in a Cohort of Prediabetes
Endocrine, Metabolic & Immune Disorders - Drug Targets Generation of Mesenchymal Stem Cells by Blood Cell Reprogramming
Current Stem Cell Research & Therapy Role of Antioxidants, Essential Fatty Acids, Carnitine, Vitamins, Phytochemicals and Trace Elements in the Treatment of Diabetes Mellitus and its Chronic Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Fish Oil Fatty Acids as Cardiovascular Drugs
Current Vascular Pharmacology The Mechanism of Carvedilol in Experimental Viral Myocarditis
Current Pharmaceutical Design