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Effect of natural antioxidants and apocynin on LPS-induced endotoxemia in rabbit

L Lomnitskil

Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel

A Nyska

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

M Carbonatto

S Peano

LCG-RBM Instituto di Ricerche Biomediche "Antoine Marxer" S.p.A, Via Ribes 1, 10015 Colleretto Giacosa, Torino, Italy

Y Zurovskyl

M Bergman

Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel

S R Eldridge

Pathology Associates International (PAI), Maryland 21071, USA

S Grossman

Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel

The objective of this study was to compare the prophylactic effects of the natural antioxidant from spinach (NAO) and apocynin, on the hepatic oxidative stress and liver damage induced by lipopolysaccharide (LPS). Male New Zealand rabbits were challenged with LPS with or without 8 days of antioxidant pretreatment. Pretreatment with NAO, but not apocynin, significantly (p<0.05) decreased the levels of hydroperoxides and malondialdehyde (MDA) in the liver cytosolic fraction and the activity of NADPH oxidase-generated superoxide in the microsomal fraction, compared to LPS alone. The activity of glutathione peroxidase (G-POX) was significantly (p<0.05) increased in the LPS-treated group, whereas treatment with NAO, but not apocynin, significantly (p< 0.05) decreased G-POX activity. Pretreatment with the same antioxidants had no significant effects on superoxide dismutase (SOD) activity, whereas an increased level of catalase (CAT) was obtained in all LPS-treated groups. TUNEL immunohistochemical staining in the LPS-treated animals indicated that there was no increase in apoptosis outside of necrotic foci. However, apoptotic hepatocytes were observed within areas of focal necrosis in animals exposed to LPS alone or LPS plus apocynin. Hepatocyte cell proliferation was tested by the proliferating-cell nuclear antigen (PCNA) tool, which indicated a proliferative effect in the LPS group, whereas the effect disappeared in the antioxidant-treated groups. The prophylactic effect of NAO on liver pathology and the significant decreases in lipid peroxidation products and NADPH oxidase activity suggest the use of NAO as an efficient strategy for treatanent of endotoxemia.

Key Words: inflammation • liver • oxidation stress • NADPH oxidas

Human & Experimental Toxicology, Vol. 19, No. 11, 604-614 (2000)
DOI: 10.1191/096032700666138364


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