Oleuropein Group Research Articles

Oleuropein Has Modulatory Effects on Systemic Lipopolysaccharide-Induced Neuroinflammation in Male Rats

BackgroundNeuroinflammation induced by systemic inflammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-inflammatory properties; however, its effect on systemic inflammation-related neuroinflammation is unknown. ObjectivesThis study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. MethodsSix-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1) control, 2) OLE-only, 3) LPS + vehicle, 4) OLE+LPS (O-LPS), and 5) a single-dose OLE + LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fibrillary acidic protein (GFAP) and CD11b immunohistochemistry, nod-like receptor protein-3, interleukin (IL)-1β, IL-17A, and IL-4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. ResultsIn both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus (P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group (P < 0.001). Hippocampal GFAP immunoreactivity and IL-17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL-4 concentrations. ConclusionsOLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL-4 concentrations indicates the induction of an anti-inflammatory phenotype of microglia. OLE may also modulate astrocyte and IL-17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL-17A concentrations when administered with or without LPS.

Effects of Oleuropein Oral Intake on Infected Fat Grafts: Experimental Study.

The aim of this study was to evaluate the effects of oleuropein oral intake on infected fat grafts and fat graft survival. 32 Wistar albino rats were divided into four groups: 0. none treated, 1. serum oral intake, 2. antibiotic oral intake, and 3. oleuropein oral intake. The dorsal regions of the rats were separated into four quadrants as right and left cranial, and right and left caudal to determine each quadrant where fat grafts were placed. Right cranial and caudal quadrants were infected with the methicillin-susceptible Staphylococcus aureus (MSSA) strain. The left cranial and caudal quadrants were infected with the Pseudomonas aeruginosa strain. On the 7th day and end of the 3rd month, fibroblast density, inflammation, and fat survival were demonstrated immunohistochemically with FGF, CD68, and perilipin (PP), respectively. On the 7th day, for P. aureginosa-infected grafts, oleuropein was shown higher rates in CD68 and PP staining compared to the antibiotic group (p<0.05, p<0.001, respectively). At the end of the 3rd month, for P. aureginosa and S. aureus-infected grafts, the oleuropein group was demonstrated improved PP staining rates compared to the antibiotic group (p<0.01, p<0.01, respectively). Oleuropein as a natural olive leaf extract with potent antioxidant, anti-inflammatory, and antimicrobial features is an alternative and supportive agent for both treatment and prophylaxis of surgical site infections like the antibiotics of chemical synthesis. P. aeruginosa and S. aureus surgical site infections could treat and prevent safely and effectively by oleuropein, particularly in early and late periods after surgery. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Oleuropein Effect on Noise-Induced Hearing Loss.

Background : To investigate the possible protective activity of oleuropein compound on noise-induced hearing loss in rats.Methods: Twenty-eight adult male albino rats were divided into 4 groups. Control normal saline (n = 7) group was kept noise-free. Control oleuropein group (n = 7) group was kept noise-free and was administered with 50 mg/kg/day oleuropein. The experimental normal saline (n = 7) group was subjected to noise. The experimental oleuropein (n = 7) group was subjected to noise and was administered with 50 mg/kg/day oleuropein. The experimental groups were subjected to 4 kHz octave noise with a frequency of 120 dB Sound Pressure Level (SPL) for 4 hours. Hearing level measurements were performed with auditory brainstem response and distortion-product otoacoustic emission tests before and after the 1st, 7th, and 10th day of the noise exposure. On the 10th day, rats were sacrificed. The temporal bones of the rats were removed and the cochlea and spiral ganglion cells were evaluated using hematoxylin–eosin staining under light microscopy.Results: Better hearing thresholds were achieved in the experimental oleuropein group compared to the experimental normal saline group at 8 kHz, 12 kHz, 16 kHz, and 32 kHz frequencies (P < .05). Although no statistically significant difference was found between the groups, in the experimental normal saline group, the percentage of damaged spiral ganglion cells was higher than the experimental oleuropein group.Conclusion: Our findings suggest that oleuropein may have a partial protective effect against noise-related hearing loss. However, further research with higher doses is needed to justify this protective effect.

Therapeutic Effects of Oleuropein in Improving Seizure, Oxidative Stress and Cognitive Disorder in Pentylenetetrazole Kindling Model of Epilepsy in Mice.

Prolonged epileptic seizures are the cause of neuronal death and brain damage. Lesions in different regions of the brain can lead to memory loss and cognitive disorders. It is therefore essential to seek out new neuroprotective drugs. Our aim was to investigate the therapeutic effects of oleuropein in improving seizure, oxidative stress, and cognitive disorder in pentylenetetrazole (PTZ) kindling model of epilepsy in mice. Mice were randomized to four groups; negative control group intraperitoneally receiving PTZ for 10 days, oleuropein group receiving oleuropein (20 mg/kg) 30 min before PTZ administration, positive control group receiving diazepam 30 min before PTZ administration and flumazenil group receiving flumazenil and then oleuropein 30 min before PTZ administration. Epilepsy severity was investigated after final administration of PTZ. Then hippocampal tissues were removed and stored at -70 °C until measurements of the interleukin-1 (IL-1) and glutamate transporter 1 (GLT-1) gene expression were conducted. Oleuropein treatment caused a significant increase in seizure latency and a significant decrease in total frequencies of head ticks, head and upper limbs seizures, the whole body seizures, frequent spinning and jumping and tonic seizures in PTZ receiving mice. IL-1 expression decreased in oleuropein group and GLT-1 levels did not change significantly in this group. Oleuropein treatment caused significant improvement of passive avoidance memory in PTZ receiving mice in shuttle box. Oleuropein can decrease PTZ-induced seizures and memory disorders due to its antioxidant and anti-inflammatory properties and is thus recommended to be used for production of anti-epileptic drugs.

The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis.

Unilateral ureteral obstruction (UUO) induces kidney injury. Oleuropein as a major compound of olive leaves modulates the inflammatory parameters and decreases oxidative stress. Accordingly, we evaluate the renoprotective effect of oleuropein against 3-day UUO rats. Forty rats were randomly divided into five groups (n = 8) including control, UUO and UUO + oleuropein groups (50, 100 and 200mg/kg). UUO model was induced by left ureter ligation and continued for 3-day. Rats were treated synchronic daily for 3-day, then mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), serum creatinine level, and also superoxide dismutase (SOD), glutathione peroxidase (GPx) activity levels and malondialdehyde (MDA) concentration (in the obstructed kidney) were measured. The western blotting method was applied to evaluate the Bax, Bcl-2, cleaved caspase-3 and TNF-α proteins expression level. The hematoxylin and eosin method was applied to evaluate the kidney tissue damage score (KTDS). UUO significantly increased RVR, KTDS, and MDA, cleaved caspase-3, Bax, serum creatinine and TNF-α protein levels (P < 0.05), and also significantly decreased RBF, SOD, and GPx and Bcl-2 protein expression levels (P < 0.001) in the obstructed kidney and oleuropein (200mg/kg) significantly ameliorated the changes induced by UUO. Our findings showed that oleuropein has a renoprotective effect against 3-day UUO. The mechanisms underlying the observed effects may be related to its antioxidative stress, anti-apoptotic, and anti-inflammatory effects.

The protective role of oleuropein against diethylnitrosamine and phenobarbital induced damage in rats

Abstract Objective Liver cancer is amongst the most lethal cancers worldwide. Diethylnitrosamine (DEN) and phenobarbital (PB) are common agents that form reactive oxygen species (ROS). Oleuropein (OLE) has efficient biological properties and used as a therapeutic agent. In this study, we aimed at investigating OLE against DEN + PB induced liver damage. Methods Adult Sprague-Dawley rats were divided into 5 groups (n = 10): Control, DEN, DEN + PB, DEN + PB + OLE and OLE. DEN, DEN + PB, DEN + PB + OLE groups were administered a single dose of 150 mg/kg DEN. After two weeks, DEN + PB and DEN + PB + OLE groups received 500 ppm of PB. 10 mg/kg/day of OLE was orally administered to DEN + PB + OLE and OLE groups. Biochemical and histopathological changes evaluated after the 8 weeks study. Results DEN and PB application with OLE treatment resulted significant differences, alone or combined. Although there was a significant difference among the groups in terms of liver GSH and MDA levels and CAT activities, there was no significant difference among the groups in SOD activity. In the liver sections of the DEN, DEN + PB and OLE groups, increase in some histopathological findings and TUNEL positive cells were increased compared to the control group. Conclusion OLE can be used as a protector against the effects of carcinogens causing liver damage.

Oleuropein suppresses oxidative, inflammatory, and apoptotic responses following glycerol-induced acute kidney injury in rats

AimHere, we evaluated the possible protective effects of oleuropein, the major phenolic constituent in virgin olive oil against glycerol-induced acute kidney injury (AKI) in rats. Main methodsTwenty-eight Sprague Dawley rats were allocated equally into four groups as follows: control group, oleuropein group (50 mg/kg body weight), AKI group and the oleuropein + AKI group. AKI was induced by injecting 50% glycerol (10 ml/kg body weight) intramuscularly. Key findingsGlycerol injection increased the kidney relative weight as well as rhabdomyolysis (RM)- and AKI-related index levels, including the levels of creatine kinase, lactate dehydrogenase, creatinine, urea, and Kim-1 expression. Additionally, alteration in oxidative conditions in renal tissue was recorded, as confirmed by the elevated malondialdehyde and nitric oxide levels and the decreased glutathione content. Concomitantly, the protein and mRNA expression levels of antioxidant enzymes were suppressed. Moreover, Nfe2l2 and Hmox1 mRNA expression was also downregulated. Glycerol triggered inflammatory reactions in renal tissue, as evidenced by the increased pro-inflammatory cytokines and Ccl2 protein and mRNA expression, whereas myeloperoxidase activity was increased. Furthermore, glycerol injection enhanced apoptotic events in renal tissue by increasing the expression of the pro-apoptotic proteins and decreasing that of anti-apoptotic. However, oleuropein administration reversed the molecular, biochemical, and histological alterations resulting from glycerol injection. SignificanceOur data suggest that oleuropein has potential as an alternative therapy to prevent or minimize RM incidence and subsequent development of AKI, possibly due to its potent anti-stress, anti-inflammatory, and anti-apoptotic effects.

Evaluation of the effect of oleuropein on alveolar bone loss, inflammation, and apoptosis in experimental periodontitis.

The present study aimed to evaluate the effects of oleuropein on ligature-induced alveolar bone loss. In this respect, osteoblastic activity, osteoclastic activity, inflammatory markers, and apoptosis were evaluated. Oleuropein is a flavonoid, which has potent anti-inflammatory and bone-protective effects. Thirty-two Wistar rats were divided into four experimental groups as following: control (C, n=8) group; periodontitis (P, n=8) group; periodontitis and low-dose oleuropein group (12mg/kg/day oleuropein, LDO group, n=8); and periodontitis and high-dose oleuropein group (24mg/kg/day oleuropein, HDO group, n=8). Periodontitis was induced via ligatures. Study period was 14days, and animals were sacrificed at end of this period. Mandibles were examined via a stereomicroscope and underwent histological procedures. Osteoblast, tartrate-resistant acid phosphatase (TRAP)-positive osteoclast, and inflammatory cell counts were determined in hematoxylin-eosin stained sections. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-4, the cluster of differentiation (CD)-68, cysteine-aspartic proteases-3 (Caspase 3), and B-cell lymphoma-2 (Bcl-2) expressions were evaluated via immunohistochemistry. Periodontitis group had highest alveolar bone loss, and these levels significantly decreased in LDO and HDO groups. Both 12 and 24mg/kg oleuropein groups significantly increased osteoblast cell counts and decreased TRAP-positive osteoclast and inflammatory cell counts. BMP-4 and bcl-2 expressions were elevated in oleuropein groups while caspase-3 expressions decreased. iNOS and CD68 were higher in periodontitis group compared to control group, but there was no significant difference between other groups. Oleuropein successfully decreased alveolar bone loss as a result of decreased osteoclastic activity, inflammation, and apoptosis and increased osteoblastic activity.

Protective Effects of Oleuropein Against Cerebral Ischemia/Reperfusion by Inhibiting Neuronal Apoptosis.

BackgroundIn this study, we investigated the potential neuroprotective effect of oleuropein (OLE) on apoptotic changes via modulating Akt/glycogen synthase kinase 3 beta (Akt/GSK-3β) signaling in a rat model of cerebral ischemia/reperfusion injury (IRI).Material/MethodsSprague-Dawley male rats (12 weeks, n=200) were randomly assigned to 5 groups: sham group, vehicle (IRI+ vehicle) group, OLE (IRI+OLE) group, OLE+LY294002 (IRI+OLE+LY294002) group, and LY294002(IRI+LY294002) group. The rats were subjected to cerebral ischemia/reperfusion injury (IRI) model and treated once daily for 5 days with vehicle and OLE (100 mg/kg via intraperitoneal injection) after IRI injury. LY294002 (0.3 mg/kg) was intraperitoneally injected once at 30 min after IRI injury. Brain edema, neurological deficit, rotarod latencies, and Morris water maze (MWM) performance were evaluated after IRI. The number of dead cells were assayed by TUNEL staining. Western blot was used to detect the expression of Bcl-2, Bax, cleaved caspase-3 (CC3), neurotrophic factors, and the phosphorylation levels of Akt and GSK-3β.ResultsCompared with the vehicle group, brain water content, neurological deficits, rotarod latencies, and escape latency following IRI were reduced in the OLE group. Cell apoptosis and reduced neurotrophic factor caused by IRI was also attenuated by OLE. Furthermore, increased p-Akt and decreased p-GSK-3β were caused by OLE, which were associated with decrease of Bax/Bcl-2 ratio and the suppression of Caspase-3 activity after IRI. Importantly, all the beneficial effects of OLE in the vehicle group were abrogated by PI3K inhibitor LY294002.ConclusionsCerebral ischemia was protected by OLE via suppressing apoptosis through the Akt/GSK-3β pathway and upregulating neurotrophic factor after IRI.

Therapeutic effects of oleuropein on cisplatin-induced pancreas injury in rats.

Cisplatin (CIS) is an influential chemotherapeutic agent in the treatment of several types of malignant solid tumors, but its clinical use is related with ototoxicity. Oleuropein (OLE) is a natural antioxidant and scavenging free radicals. Here, we first explore the efficacy of OLE in pancreas against to the toxicity of CIS and also analyses its mechanism. Fifty-six Sprague-Dawley rats were equally divided into eight groups, including, control group which received 7 mg/kg/day CIS intraperitoneally (i.p.) for 24 h, groups treated with doses of 50, 100, and 200 mg/kg OLE i.p. for 3 days, and groups which received same dose of CIS with three doses of OLE. After the treatments, animals were sacrificed. The oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), total oxidative stress (TOS), total antioxidant status (TAS), and malondialdehyde (MDA) levels were evaluated in the pancreas. The histopathology of the pancreas was examined using three different staining methods: hematoxylin-eosin, periodic acid-Schiff, and alcian blue. Serum was provided to assess pancreatic function the lipase and amylase values. The results showed that CIS significantly increased the level of TOS, MDA, and 8-OHdG in tissue as compared to the control group. Moreover, severe tissue damages were detected in the pancreas. Whereas, OLE at high dose significantly decreased the formations of 8-OHdG, the level of MDA, and increased levels of TAS in tissue samples. In the CIS group, the levels of amylase and lipase increased compared with the control group. However, there were statistically significant differences among the CIS group and the CIS + OLE groups in the values of both amylase and lipase. In addition, histopathological findings observed in CIS group in the pancreatic tissue alleviated in CIS + OLE groups. We hope that the results of this study will provide an impetus for future investigations of novel treatment strategies for OLE in pancreas due to CIS.

Impact of high-dose oleuropein on cisplatin-induced oxidative stress, genotoxicity and pathological changes in rat stomach and lung

The current systemic treatments of the various solid tumors involve Cisplatin (CIS)-based chemotherapy. Due to its cytotoxicity, this approach is limited. Moreover, the safety of CIS is only discussed especially in breast and stomach cancers. Therefore, we, for the first time, explored the restorative efficacy of oleuropein (OLE), in stomach and lung injuries induced by CIS. Sprague-Dawley rats were divided into eight groups: control CIS, OLE and CIS + OLE. Single dose of (7 mg/kg) CIS was administered intraperitoneally to CIS and CIS + OLE groups. After 24 h, 50, 100 and 200 mg/kg OLE was given for three consecutive days to OLE and CIS + OLE groups. The 8-OH-dG, total oxidative/antioxidant status (TOS/TAS) and malondialdehyde (MDA) levels were evaluated and histopathological analyses were performed on the studied tissues. The results indicated that CIS significantly increased 8-OH-dG, MDA and TOS levels and caused severe tissue damages. However, high dose of OLE induced a significant decrease in the 8-OH-dG, MDA levels, an increase in TAS levels and it restores CIS-induced tissue damages. We hope that the results of this study will provide an impetus for future studies on novel therapeutic strategies including the protective use of oleuropein in gastric and lung cancers due to chemotherapy.

Effect of oleuropein on myocardial dysfunction and oxidative stress induced by ischemic-reperfusion injury in isolated rat heart

BackgroundStudies have reported antioxidant effect of oleuropein in isolated rat heart. ObjectiveThis study was conducted to investigate whether perfusion of isolated rat heart with oleuropein, before induction of ischemia or at the onset of reperfusion, had any effect on the hemodynamic parameters, infarct size and biochemical factors following ischemic – reperfusion injury. Materials and methodsForty-eight male Wistar rats were divided into 6 groups: the control groups (Con-P and Con-T groups), O10-P and O50-P groups perfused with 10 and 50 μg/g heart oleuropein 5 min before the induction of ischemia and O10-T and O50-T groups perfused with 10 and 50 μg/g heart oleuropein at the beginning of the reperfusion, respectively. All hearts were subjected to 30 min global ischemia and 90 min reperfusion. Hemodynamic parameters were monitored throughout the experiment. The creatine kinase (CK) and malondialdehyde (MDA) level of coronary outflow were assayed and the infarct size measured at the end of reperfusion. ResultsWe found hemodynamic parameters namely heart rate, left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), ±dp/dt and coronary outflow significantly improved in all groups that received oleuropein compared to the control groups. Also, the infarct size was smaller and the coronary outflow levels of CK and MDA were lower in the oleuropein groups compared to the control groups. ConclusionsThe findings suggest that perfusion of isolated rat heart with oleuropein would lead to improved myocardial dysfunction following ischemic-reperfusion injury. Our findings confirm the antioxidant potential of oleuropein.

Oleuropein Attenuates Deltamethrin-induced Apoptosis in Rat Cerebellar Purkinje Neurons

Corresponding Author: Ali Reza khalatbary Molecular and Cell Biology Research Center, Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Phone: +98 1133200894 E-mail: khalat90@yahoo.com Abstract Background: Deltamethrin (DM) is a synthetic pyrethroid insecticide that can elicit neurotoxicity, and lead to apoptosis. There is accumulating evidence that oleuropein (OE) has anti-apoptotic effect. This study aimed at determining the DM toxicity and anti-apoptotic effect of OE pretreatment in cerebellar Purkinje neurons. Materials and Methods: Rats were randomly divided into four groups as follow: DM treated group (12.5 mg/kg; single dose), OE treated group (20 mg/kg per day), DM plus OE treated group, and vehicle group. Sections of cerebellum were taken 24 hours after deltamethrin injection and studied for histopathological and immunohistochemistry assessments. Results: Further characteristics of degeneration in Purkinje neurons were observed in DM group compared with DM plus OE group. Compared with DM group (9.56±1.69), the positive staining for Bax in Purkinje neurones decreased in DM plus OE group (2.99±0.50) but upper than OE (0.72±0.15) and vehicle (0.57±0.03) groups. Compared with DM group (0.50±0.05), the positive staining for Bcl-2 in Purkinje neurons increased in DM plus OE group (3.29±0.18) but lower than OE (4.38±0.80) and vehicle (5.87±1.93) groups. Conclusions: Our results suggest that DM induces apoptosis in Purkinje cells which is subsided by oleuropein.

Protective Role of Oleuropein against Acute Deltamethrin-Induced Neurotoxicity in Rat Brain.

Background:Deltamethrin (DM) is a synthetic pyrethroid insecticide that can elicit neurotoxicity, leading to apoptosis. There is accumulating evidence that oleuropein (OE) has anti-apoptotic effect. The purpose of this study was to determine the anti-apoptotic effect of OE pretreatment in the neuronal cells of cerebral cortex. Methods:Rats were randomly divided into four groups each containing five rats: DM-treated group (12.5 mg/kg, a single dose), OE-treated group (20 mg/kg per day), DM + OE-treated group, and vehicle group. Sections of the brain were obtained 24 hours after DM injection and studied for histopathological and immunohistochemistry assessment. Results:The histopathological assessments showed lesser characteristics of neural degeneration in DM + OE group compared with DM group. Greater Bcl-2 and attenuated Bax expression could be detected in the DM + OE treated-mice compared with DM group. Conclusion:The results suggested that DM-induced neurotoxicity can be subsided by OE.

The olive constituent oleuropein prevents cardiac doxorubicin-induced changes in eNOS expression, apoptotic mediators and energy metabonomics in rats

Purpose: Doxorubicin (DXR) causes cardiotoxicity through nitro-oxidative stress, but the exact pathogenesis is not fully elucidated. Oleuropein (OLEU), a polyphenolic constituent of olive and its products, prevents acute and chronic DXR-induced cardiotoxicity. We evaluated mechanisms potentially involved in chronic DXR cardiotoxicity, including eNOS, pro-apoptotic mediators and energy metabonomics as well as OLEU impact on these mechanisms. Methods: Ninety rats were divided into 6 groups: Control group, no treatment; OLEU-70 and OLEU-140 groups, 70 and 140 mg/kg of OLEU, respectively, given intraperitoneally (ip) for 2 weeks; DXR group, 18mg/kg of DXR ip, divided into 6 equal doses and given over a period of 2 weeks; OLEU-70-DXR and OLEU-140-DXR groups, combined OLEU and DXR as previously described. The rats were finally sacrificed and the hearts were excised for tissue assessment of eNOS, Akt and AMPK by immunohistochemistry and Western-Blot. NMR spectra of tissue extracts was also recorded and analyzed further by multivariate statistics. Results: DXR group had lower eNOS, Akt and AMPK activation compared to controls and all OLEU groups. The NMR-based metabonomic study depicted differences in the metabolic profile of DXR compared to all other groups (Figure) suggesting an impaired energy metabolism in this group and rehabilitation with OLEU administration. The inhibition of AMPK activation by DXR, correlated with the change in the profile of cardiac energy substrate utilization with a decrease in glucolysis and fatty acids oxidation. ![Figure][1] Conclusion: Impaired eNOS, Akt and AMPK expression and cardiac energy metabolism disruption is involved in chronic DXR cardiotoxicity; OLEU prevented those changes, thus providing a potential protective agent against DXR-induced cardiomyopathy. [1]: pending:yes

Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats

Purified oleuropein from olive leaf extract has been shown to have antioxidant effects in our recent studies. Thus, the aim of this study was to assess the antioxidant abilities of oleuropein in comparison with ranitidine in ethanol-induced gastric damages via evaluation of ulcer index inhibition, antioxidant enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague-Dawley rats were divided into seven equal groups as follows: control group, ethanol group (absolute ethanol 1 ml/rat), oleuropein group (12 mg/kg), and oleuropein (6, 12, and 18 mg/kg) plus ethanol groups, as well as ranitidine (50 mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18 mg/kg) significantly increased the ulcer index inhibition (percent), in comparison with oleuropein (6 mg/kg). Glutathione peroxidase (GPx) activity was significantly lower in the ethanol group when compared with the other groups whereas, treatment of rats with oleuropein (12 mg/kg) significantly increased glutathione content in gastric tissue when compared with the other groups, and lipid peroxidation was significantly reduced in the oleuropein- (12 and 18 mg/kg) and ranitidine-treated animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much higher in oleuropein-treated rats than the ethanol group, and although there was a moderate increase in SOD and CAT activities in ranitidine-treated rats, the differences were not significant. These findings suggest that oleuropein has beneficial antioxidant properties against ethanol-induced gastric damages in the rat. Therefore, it seems that a combination regimen including both antioxidant and antisecretory drugs may be beneficial in prevention of ethanol-mediated gastric mucosal damages.

Oleuropein protects against ethanol-induced oxidative stress and modulates sperm quality in the rat testis

The aim of the present study was to evaluate the antioxidant properties of oleuropein on ethanol-induced oxidative stress in the rat testis. 32 adult male Sprague–Dawley rats were divided into four equal groups: the first group as a control, the second group of rats were given ethanol (4 g/kg), the third group received oleuropein (15 mg/kg), and the fourth group of rats were supplemented of oleuropein (15 mg/kg) and after 120 min were ingested via ethanol (4 g/kg) orally. Oleuropein could prevent the reduction of motility and plasma membrane integrity of the spermatozoa against ethanol-induced oxidative stress in treated rats (P < 0.05). While, thiobarbituric acid reactive substances (as a lipid peroxidation marker) concentration was decreased significantly in the oleuropein plus ethanol group compared to the ethanol group (P < 0.05). Notably, glutathione peroxidase and superoxide dismutase activity increased significantly in the ethanol-treated animals compared to controls and total glutathione (GSH-content) increased significantly in ethanol-treated rats compared to the oleuropein group. Our findings suggest that oleuropein possesses beneficial antioxidant effects on ethanol-induced sperm toxicity, subsequently enhancing sperm motility and plasma membrane integrity.

Oleuropein on lipid and fatty acid composition of rat heart

Male rats of the Wistar strain were given oleuropein for 3 weeks at a dose of 25 or 50 mg/kg of body weight. Heart samples were analyzed for the lipid composition by the Iatroscan TLC FID technique and for the fatty acid profile of neutral and polar lipids by the capillary gas chromatography. In addition, the oleuropein, α- and β-tocopherol content in the total heart lipids were also determined. Oleuropein treatment increased the level of cholesteryl esters, but it decreased the level of triacylglycerols, in the heart of animals. Sphingomyelin and lysophosphatidylcholine levels were only higher in the 50 mg oleuropein group. There was also a significant reduction in the linoleic acid content in the heart polar lipids of oleuropein-treated animals. As consequence of treatment, oleuropein was incorporated into the heart of animals in a concentration-dependent manner, whereas the α- and β-tocopherol content decreased. Oleuropein may therefore act as a substitute of the natural antioxidants in heart, with minor changes in the unsaturated lipids.