Radical-scavenging
antioxidants, as part of the cellular defense system, function to inhibit the formation and propagation of
free radicals and
active oxygen species formation. In previous studies we demonstrated that
endotoxin lipopolysaccharide (LPS) promotes oxidative stress and associated pathological changes in a rat model and that use of selected
antioxidants was effective in reducing LPS-related lipid peroxidation product formation in the liver, as well as LPS-related pathological changes in different organs. In this study, several toxicological parameters (ie, clinical signs, blood chemistry, and histopathological changes) were compared among groups of male New Zealand rabbits injected with LPS following prophylactic pretreatment with either of 2
antioxidants, a group injected with LPS without pretreatment with
antioxidants, groups injected with either of the 2
antioxidants only, and an untreated control group. The
antioxidants used were a water-soluble natural
antioxidant (
NAO) from spinach and the
NADPH oxidase inhibitor,
apocynin. Exposure to LPS alone was associated clinically with depression,
tachypnea, outer ear vasodilation, and iris congestion; biochemically with a significant increase in blood total
bilirubin,
transaminase activity, and
glucose, total
cholesterol, and
triglyceride levels; macroscopically with multiple whitish areas in the liver; and histologically with hepatocellular focal
necrosis and acute
inflammation, thymic and splenic lymphoid
necrosis and depletion, acute
uveitis and
hemorrhages in the ciliary processes, and decreased adrenal cortical cytoplasmic vacuolation considered consistent with depletion of steroidal
hormone contents. The
NAO had more effective prophylactic capacities than the
apocynin. The protective effects were obvious in all investigated parameters. The results indicate the possible therapeutic efficacy of
NAO in the treatment of clinical
endotoxemia associated with gram-negative bacterial
sepsis that is known to be associated with oxidative stress.