Hepatic
phosphatidylcholine hydroperoxide (
PCOOH) was studied intensively to delineate its role in the altered pathophysiology of
liver failure associated with endotoxemic
shock.
Endotoxemia was induced by cecal
ligation and
puncture (CLP) in three models using rats. Model 1 consisted of normal healthy rats; model 2, cirrhotic rats; and model 3, rats treated with
catalase and
superoxide dismutase (SOD). Samples were taken before CLP, then 12 h and 24 h following CLP. A progressive and significant increase in serum
endotoxin was seen in all models; however, a significantly low energy charge (EC) and high
PCOOH were seen in models 1 and 2, whereas no change was observed in model 3. The regional blood flow remained unchanged throughout the experiment in models 1 and 3, but not in model 2. An initial increase in
alpha-tocopherol was seen in model 1. The survival rate was markedly better in model 3 than in models 1 or 2. The fall in EC corresponded to the increase in serum
endotoxin as well as to the increase in tissue
PCOOH in models 1 and 2. It was more likely that the elevated lipid peroxidation in model 1 resulted from
endotoxemia rather than from tissue hypoperfusion. The early increase in
alpha-tocopherol that occurred in models 1 and 2, but not in model 3, indicated the antiradical defense response to oxidative injury. Thus,
antioxidant therapy significantly improved the survival rate and tissue
adenine nucleotide level in spite of the increased serum
endotoxin level.