The protective effects of hydroxyethyl
starch-conjugated
deferoxamine (
HES-DFO), a macromolecular
iron chelator, on the initial pathophysiological cascade in
septic shock were evaluated following cecal
ligation puncture (CLP) in rats. Animals were given an intravenous dose of 3.0 mL of either vehicle (HES) or
HES-DFO immediately following completion of the CLP procedure. Animals were sacrificed 30, 60, 120, and 240 min following CLP, and samples of lung, kidney, bowel, and liver were collected for subsequent analysis of
glutathione,
myeloperoxidase, and evidence for lipid peroxidation based on measurement of
thiobarbituric acid reactive substances and conjugated dienes. In addition, the
endotoxin levels were determined in the plasma and histomorphological examination was conducted on tissue samples collected at each time point. At almost all time points, a reduction in lipid peroxidation was noted in the
HES-DFO-treated rats (p < .05).
Glutathione and myoloperoxidase levels were less affected. Lung tissue from animals receiving HEs demonstrated marked microatelectases, septal destruction, and splicing of basal membranes, which were greatly attenuated in animals having received
HES-DFO. Similarly, tubulotoxic and mitochondrial damages observed in kidney samples from HES-treated animals were noticeably reduced in the animals having received the
chelator. Liver and gut samples demonstrated unspecific inflammatory injury in both groups of animals. In summary,
oxygen radical-mediated tissue damage occurs rapidly following CLP-induced
sepsis. Based on histological and biochemical endpoints, treatment with the polymeric
iron chelator,
HES-DFO, significantly attenuates systemic
oxidant injury, the degree of protection being most impressive in the lung and kidney.