Therapeutic Use of Antioxidants in Sepsis

Andre   L.   Rosario; Luciano   C.P.   Azevedo

Abstract

Sepsis is one of the most studied diseases in intensive care medicine nowadays, mainly due to the severe morbidity associated with this condition. Among the several mediators evaluated in the context of sepsis, the study of reactive oxygen and nitrogen species has achieved considerable interest, mostly regarding their effects in direct cytotoxicity as well as altered cell signaling. These compounds have also been associated with vascular and organ dysfunction of sepsis. The discovery of precise mechanisms of free radical-induced organ dysfunction may lead to the discovery of therapeutic strategies able to reduce the severe effects of sepsis in the organism. In this context, the administration of antioxidants has been tested in experimental and clinical studies of sepsis in order to restore their adequate levels that are frequently diminished during the course of disease. This review will focus on mechanisms associated with increased oxidative stress in sepsis, as well as therapeutic strategies concerning antioxidant therapy during sepsis and multisystem organ failure. The most recent patents related to the clinical use of antioxidants in this field will also be discussed.

Keywords: Sepsis, reactive oxygen species, nitric oxide, antioxidants, free radicals, superoxide, alpha-tocopherol, superoxide dismutase, mitochondria