Role of Free Radicals in Sepsis: Antioxidant Therapy

Author(s): V. M. Victor, M. Rocha, J. V. Esplugues, M. De la Fuente

Journal Name: Current Pharmaceutical Design

Volume 11 , Issue 24 , 2005

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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

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Article Details

Year: 2005
Page: [3141 - 3158]
Pages: 18
DOI: 10.2174/1381612054864894
Price: $65

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