Thgoal of this study was to evaluate the efficacy of the
antioxidant olive constituent,
oleuropein, on
infarct size, oxidative damage, and the metabolic profile in rabbits subjected to
ischemia.
Oleuropein, 10 or 20 mg/(kg x d), was administered to 8 groups that consumed a normal or hypercholesterolemic diet for 6 wk or only the higher dose for 3 wk. Circulating levels of
malondialdehyde,
protein carbonyl, nitrite+nitrate,
cholesterol,
triglycerides, SOD activity, and the metabolic profile were measured using 1H NMR spectra. In rabbits that consumed the normal diet, the
infarct size (percentage of
infarct to risk areas) was reduced by the administration of 10 mg
oleuropein/(kg x d) (16.1 +/- 2.9%) or 20 mg
oleuropein/(kg x d) for 3 wk (21.7 +/- 2.2%) or for 6 wk (24.3 +/- 1.3%) compared with the control group (48.05 +/- 2.0%, P < 0.05). Only the higher dose of 20 mg/(kg x d) reduced the
infarct size in hypercholesterolemic rabbits (34.7 +/- 4.4% for 6 wk and 34.8 +/- 6.1% for 3 wk) compared with the
cholesterol-fed control group (52.8 +/- 2.4%, P < 0.05).
Oleuropein decreased the plasma lipid peroxidation product and
protein carbonyl concentrations compared with the control groups, in which these factors increased relative to baseline due to
ischemia and reperfusion. Furthermore, in rabbits administered
oleuropein, RBC
superoxide dismutase activity did not change during
ischemia and reperfusion. This activity was significantly higher than in both control groups in which it was reduced by
ischemia and reperfusion compared with baseline. Treatment for 6 wk with both doses of
oleuropein reduced total
cholesterol and
triglyceride concentrations. 1H NMR spectra revealed a different profile of glycolysis metabolites in the
oleuropein-treated groups compared with the controls.
Oleuropein, for 3 or 6 wk, reduced the
infarct size, conferred strong
antioxidant protection and reduced the circulating
lipids. This is the first experimental study in vivo that suggests the possibility of using an olive constituent in the treatment of
ischemia.