The olive constituent oleuropein exhibits anti-ischemic, antioxidative, and hypolipidemic effects in anesthetized rabbits.
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.
Andreadou
Ioanna
I
Second University Department of Cardiology, Medical School, Attikon General Hospital, University of Athens, Athens, Greece. jandread@pharm.uoa.gr
Iliodromitis
Efstathios K
EK
Mikros
Emmanuel
E
Constantinou
Maria
M
Agalias
Apostolos
A
Magiatis
Prokopios
P
Skaltsounis
Alexios Leandros
AL
Kamber
Elli
E
Tsantili-Kakoulidou
Anna
A
Kremastinos
Dimitrios Th
DT
D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D000975:Antioxidants / Q000302:isolation & purification / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D057888:Iridoid Glucosides; D039823:Iridoids; D008055:Lipids / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D031658:Olea; D008517:Phytotherapy; D011714:Pyrans / Q000302:isolation & purification / Q000627:therapeutic use*; D011817:Rabbits
D000959:Antihypertensive Agents; D000975:Antioxidants; D000960:Hypolipidemic Agents; D057888:Iridoid Glucosides; D039823:Iridoids; D008055:Lipids; D011714:Pyrans; C002769:oleuropein; D008315:Malondialdehyde