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 treatment of
endotoxemia.