oleuropein and Acute-Disease

Oleuropein, the major secoiridoid in olive tree leaves, possesses a wide range of health promoting properties. It has recently been shown to exhibit anti-inflammatory activity. We have evaluated the effect of oleuropein on dextran sulfate sodium (DSS)-induced experimental colitis in mice in order to provide insight into its mechanisms of action. Oral administration of oleuropein notably attenuated the extent and severity of acute colitis while reducing neutrophil infiltration; production of NO, IL-1β, IL-6, and TNF-α; expression of iNOS, COX-2, and MMP-9; and the translocation of the NF-κB p65 subunit to the nucleus in colon tissue. In LPS-stimulated peritoneal macrophages, the oleuropein metabolite, hydroxytyrosol, was shown to inhibit NO production, iNOS expression, NF-κB p65 subunit translocation, mRNA expression, and the release of IL-1β, IL-6, and TNF-α. These results suggest that the effect of oleuropein on DSS-induced colitis is associated with a decrease in the production of interleukins and expression of proteins, principally through reduction of NF-κB activation.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Colitis; Cytokines; Dextran Sulfate; Female; Iridoid Glucosides; Iridoids; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Nitric Oxide; Phenylethyl Alcohol; Pyrans

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