Scavengers prevent lung injury but do not improve the survival during sepsis in rats
© BioMed Central Ltd. 2004
Published: 15 March 2004
To assess the efficacy of scavengers on lung injury during intra-abdominal sepsis in rats.
The Sprague–Dawley rats (male, 200–250 g) underwent cecal ligation and puncture (CLP); the cecum was punctured with a 18-gauge needle through and through to obtain two holes, and gentle pressure was applied on the ligated cecum to exteriorize a small amount of feces, followed by closure of the abdominal incision. Five hours later, these animals were then injected intraperitoneally with polyethylene glycol absorbed catalase; scavengers of hydrogen peroxide (A group), dimethyl sulfoxide; scavenger of hydroxyl radicals (B group), polyethylene glycol absorbed superoxide dismutase; scavengers of superoxide ions, or saline (control group). Survival was evaluated for 24 hours after CLP, and then surviving animals were sacrificed with carbon dioxide inhalation for outcome. The lung protein synthesis was evaluated with a nitrotyrosine/tyrosine ratio and oxidative damage in DNA was evaluated with the 8-oxodeoxyguanosine/deoxyguanosine ratio in the homogenized lung tissue, which were measured by HPLC. Neutrophil accumulation in the lung was evaluated with myeloperoxidase activity (MPO), intracellular adhesion molecule-1 (ICAM-1) expression on these cells in the lung was evaluated with pathological examination.
MPO, ICAM-1 expression, the nitrotyrosine/tyrosine ratio and the 8-oxodeoxyguanosine/deoxyguanosine ratio were significantly lower in all the scavenger-treated groups (A, B, C) than in the saline-treated group. However, there was no difference in the survival rate in all the groups (A, 33.3%; B, 20%; C, 0%; control, 27.7%).
Scavengers attenuate neutrophil accumulation and lung injury, but do not improve survival. These results suggest that factors other than lung injury may be responsible for mortality in this rat model of sepsis. However, additional studies of both superoxide in the early phase and late assessment of outcome are indicated.