Role of free radicals in sepsis: antioxidant therapy.

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 factor-alpha (TNFalpha) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of the Gram-negative 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-kappaB (NF-kappaB) 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.

journal_name

Curr Pharm Des

authors

Victor VM,Rocha M,Esplugues JV,De la Fuente M

doi

10.2174/1381612054864894

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

3141-58

issue

24

eissn

1381-6128

issn

1873-4286

journal_volume

11

pub_type

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