Antioxidant treatment reverses organ failure in rat model of sepsis: role of antioxidant enzymes imbalance, neutrophil infiltration, and oxidative stress.
BACKGROUND
Some of the postulated molecular mechanisms of sepsis progression are linked with the imbalance between reactive oxygen species (ROS) production and its degradation by cellular antioxidant pathways. Some studies have correlated plasma oxidative stress, inflammatory markers, and clinical markers of organ failure, but none performed this in a systematic way, determining in situ oxidative and inflammatory markers and correlating these with markers of organ failure.


METHODS
Rats subjected to cecal ligation and puncture (CLP) were treated with basic support or antioxidants and killed 12 h after to determine thiobarbituric acid reactive species (as an index of oxidative damage), superoxide dismutase (SOD), catalase (CAT), and myeloperoxidase (MPO) (as an index of neutrophil infiltration) in the kidney and lung. In addition, protein content in bronchoalveolar lavage fluid (as an index of lung alveolo-capillary dysfunction) and plasma urea (as an index of kidney injury) were measured at the same time.


RESULTS
In the CLP group, we found a positive correlation between thiobarbituric acid reactive species (TBARS) and markers of organ injury in lung and kidney. Oxidative damage is correlated with an increase in SOD/CAT ratio only in the lung. In contrast, oxidative damage is correlated with MPO activity in the kidney, but not lung, suggesting different sources of oxidative damage depending on the analyzed organ. These reflect differences on the effects of basic support and antioxidants on organ dysfunction after sepsis.


CONCLUSIONS
Despite the general occurrence of oxidative damage in different organs during sepsis development and a positive correlation between oxidative markers and organ injury, antioxidant effects seemed to depend not only on the diminution of oxidative damage but also on its anti-inflammatory activity.
Andrades
Michael
M
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Ritter
Cristiane
C
de Oliveira
Marcos Roberto
MR
Streck
Emílio L
EL
Fonseca Moreira
José Cláudio
JC
Dal-Pizzol
Felipe
F
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism*; D003676:Deferoxamine / Q000627:therapeutic use; D004195:Disease Models, Animal; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009102:Multiple Organ Failure / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D020556:Neutrophil Infiltration / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014508:Urea / Q000097:blood
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D014508:Urea; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D000111:Acetylcysteine