Premium
Progression of oxidative and inflammatory injury in the lung after exposure to blast overpressure.
Author(s) -
Chavko Mikulas,
McCarron Richard M,
Prusaczyk W. Keith
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb121-a
Subject(s) - oxidative stress , lung , heme oxygenase , hemin , inflammation , myeloperoxidase , medicine , heme , chemistry , pathology , biochemistry , enzyme
A critical immediate determinant of survival after exposure to blast overpressure (BOP) is pulmonary damage, but mechanisms of injury and the course of recovery are not well understood. The objective of this study was to characterize the progression of oxidative and inflammatory responses in lungs and the activation of consequent protective mechanisms after exposure to medium intensity BOP. Rats were exposed to a moderate (~120 kPa) level of BOP in a pneumatically driven shock tube. At different times (2–192 hours) after exposure, lungs were examined for pathological signs of injury as well as for markers of inflammatory responses and indicators of oxidative and nitrative damage. The results showed an early activation of inflammatory response (increase of myeloperoxidase activity, cytokines and iNOS), increase in protein oxidation and nitration, and development of diffused hemorrhage in lungs. The initial phase of lung damage was followed by gradual dissolution of inflammation and oxidation that were complete by 8 days following exposure. Activation of heme oxygenase‐ 1 (HO‐1), the stress protein that is an important part of antioxidative and anti‐inflammatory mechanisms in lungs was observed 1– 2 days after exposure. To determine the potential role of HO‐1 in lung recovery after exposure to BOP, HO‐1 was induced by i.p. injection of hemin 24 h prior to exposure to BOP. Rats were exposed to ~200 kPa that produced a higher mortality rate than 120 kPa exposure. Hemin injection induced 2–3 fold increase in HO‐1 in lungs and significantly increased survival rate in animals. The finding demonstrate potential factors mitigating BOP‐induced lung injury and implicate HO‐1 in protective mechanisms against development of irreversible pulmonary damage. Supported by ONR Workunit No. 601153N.04508.518.A0406.