Effects of antioxidants apocynin and the natural water-soluble antioxidantfrom spinach on cellular damage induced by lipopolysaccaride in the rat

Oxidative damage plays a key role in septic shock induced by the endotoxin lipopolysaccaride (LPS) by enhancing the formation of reactive oxygen speci es such as superoxide anion radicals, peroxides, and their secondary produc t, malondialdehyde, especially in the liver. In this study, histopathologic changes in several organs were compared among groups of male Wistar rats t hat had been injected with LPS following prophylactic pretreatment with eit her of 2 antioxidants, a group that had been injected with LPS without pret reatment with antioxidants, an untreated control group, and groups that had been injected with either of the 2 antioxidants only. The antioxidants use d were a water-soluble natural antioxidant from spinach (NAO) and the NADPH oxidase inhibitor apocynin. Hematoxylin-and-eosin-stained slides were prep ared, and lesions were semiquantitatively scored. Exposure to LPS alone was associated with multifocal hepatocellular necrosis and acute inflammation, thymic and splenic lymphoid necrosis, ocular retinal hemorrhage and acute endophthalmitis, adrenal medullary vacuolation and necrosis and acute infla mmation, and decreased adrenal cortical cytoplasmic vacuolation (consistent with depletion of steroidal hormone contents). Results indicated that pret reatment with both antioxidants for 8 days reduced, in some organs, the nec rotic and inflammatory changes associated with the LPS challenge. These fin dings suggest a potential therapeutic application for these antioxidants in clinical sepsis.