The prophylactic effects of natural water-soluble antioxidant from spinachand apocynin in a rabbit model of lipopolysaccharide-induced endotoxemia

Radical-scavenging antioxidants, as part of the cellular defense system, fu nction to inhibit the formation and propagation of free radicals and active oxygen species formation. In previous studies we demonstrated that endotox in lipopolysaccharide (LPS) promotes oxidative stress and associated pathol ogical changes in a rat model and that use of selected antioxidants was eff ective 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 che mistry, and histopathological changes) were compared among groups of male N ew Zealand rabbits injected with LPS following prophylactic pretreatment wi th 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, ap ocynin. Exposure to LPS alone was associated clinically with depression, ta chypnea, outer ear vasodilation, and iris congestion; biochemically with a significant increase in blood total bilirubin, transaminase activity, and g lucose, total cholesterol, and triglyceride levels; macroscopically with mu ltiple whitish areas in the liver; and histologically with hepatocellular f ocal 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 wi th depletion of steroidal hormone contents. The NAO had more effective prop hylactic capacities than the apocynin. The protective effects were obvious in all investigated parameters. The results indicate the possible therapeut ic efficacy of NAO in the treatment of clinical endotoxemia associated with gram-negative bacterial sepsis that is known to be associated with oxidati ve stress.