oleuropein and Heart-Diseases

The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1 mL of DMSO by oral gavage method for 7 days. Group 2 (ketamine): on the seventh day of the study, 60 mg/kg ketamine was administered intraperitoneally. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Group 3 (oleuropein): rats were given 200 mg/kg/day oleuropein by oral gavage method for 7 days. Group 4 (oleuropein + ketamine): rats were given 1 × 200 mg/kg oleuropein by oral gavage method for 7 days. Furthermore, 60 mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-α, IL-6, NF-κB, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-α (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-κB (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-α, IL-6, COX-2, NF-κB, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSH-Px and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cardiotoxicity; Disease Models, Animal; Heart Diseases; Inflammation Mediators; Iridoid Glucosides; Ketamine; Male; Myocytes, Cardiac; Oxidative Stress; Rats, Wistar; Signal Transduction

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