3-nitrotyrosine and oleuropein

Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg(-1) × day(-1). All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing precondit

Topics: Animals; Cholesterol; Disease Models, Animal; Hypercholesterolemia; Iridoid Glucosides; Iridoids; Male; Malondialdehyde; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Olea; Oxidative Stress; Phosphatidylinositol 3-Kinases; Protective Agents; Rabbits; Signal Transduction; Tyrosine

Several olive oil phenolic compounds, such us oleuropein have attracted considerable attention because of their antioxidant activity, anti-atherosclerotic and anti-inflammatory properties. The aim of this study was to investigate the effects of oleuropein aglycone, a hydrolysis product of oleuropein, in a mouse model of carrageenan-induced pleurisy.. Mice were anaesthetized and subjected to a skin incision at the level of the left sixth intercostals space. The underlying muscle was dissected and saline or saline containing 2% λ-carrageenan was injected into the pleural cavity.. Injection of carrageenan elicited an acute inflammatory response characterized by: infiltration of neutrophils in lung tissues (P < 0.01 versus sham. P < 0.01 versus carrageenan) and subsequent lipid peroxidation (P < 0.01 versus sham. P < 0.01 versus carrageenan), increased production of tumor necrosis factor-α and interleukin-1β (P < 0.01 versus sham. P < 0.01 versus carrageenan), increased expression of adhesion molecules, increased synthesis of nitric oxide (P < 0.01 versus sham. P < 0.01 versus carrageenan), nitrotyrosine and poly-ADP-ribose (P < 0.01 versus sham. P < 0.01 versus carrageenan). Administration of oleuropein aglycone 30 min after the challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured.. Thus, we propose that olive oil phenolic constituents may be useful in the treatment of various inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carrageenan; Disease Models, Animal; Hydrolysis; Intercellular Adhesion Molecule-1; Interleukin-1beta; Iridoid Glucosides; Iridoids; Lipid Peroxidation; Lung; Male; Mice; Nitric Oxide; Olive Oil; P-Selectin; Phenols; Plant Oils; Pleurisy; Poly Adenosine Diphosphate Ribose; Pyrans; Tumor Necrosis Factor-alpha; Tyrosine

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity.

Topics: Acute Disease; Animals; Doxorubicin; Heart Diseases; Iridoid Glucosides; Iridoids; Male; Malondialdehyde; Nitrates; Nitric Oxide Synthase Type II; Nitrosation; Oleaceae; Oxidative Stress; Pyrans; Rats; Rats, Wistar; Tyrosine