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Effects of Antioxidants Apocynin and the Natural Water-Soluble Antioxidant from Spinach on Cellular Damage Induced by Lipopolysaccaride in the Rat

Bar-Ilan University, Ramat-Gan, 52900, Israel

Abraham Nyska

National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA

Varda Ben-Shaul

Bar-Ilan University, Ramat-Gan, 52900, Israel

Robert R. Maronpot

National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA

Joseph K. Haseman

National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA

Tal Levin Harrus

Harlan Biotech Israel, Rehovot, 76326, Israel

Margalit Bergman

Bar-Ilan University, Ramat-Gan, 52900, Israel

Shlomo Grossman

Bar-Ilan University, Ramat-Gan, 52900, Israel

Oxidative damage plays a key role in septic shock induced by the endotoxin lipopolysaccaride (LPS) by enhancing the formation of reactive oxygen species such as superoxide anion radicals, peroxides, and their secondary product, malondialdehyde, especially in the liver. In this study, histopathologic changes in several organs were compared among groups of male Wistar rats that had been injected with LPS following prophylactic pretreatment with either of 2 antioxidants, a group that had been injected with LPS without pretreatment with antioxidants, an untreated control group, and groups that had been injected with either of the 2 antioxidants only. The antioxidants used were a water-soluble natural antioxidant from spinach (NAO) and the NADPH oxidase inhibitor apocynin. Hematoxylin-and-eosin-stained slides were prepared, 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 inflammation, and decreased adrenal cortical cytoplasmic vacuolation (consistent with depletion of steroidal hormone contents). Results indicated that pretreatment with both antioxidants for 8 days reduced, in some organs, the necrotic and inflammatory changes associated with the LPS challenge. These findings suggest a potential therapeutic application for these antioxidants in clinical sepsis.

Key Words: Oxidative stress • necrosis • liver • adrenal • spleen • thymus

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