Oral administration of oleuropein attenuates cisplatin‐induced acute renal injury in mice through inhibition of ERK signaling

Potočnjak, Iva; Škoda, Marko; Pugel, Ester Pernjak; Peršić, Martina Pavletić; Domitrović, Robert

doi:10.1002/mnfr.201500409

Cited by 56 publications

(39 citation statements)

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“…More specifically, Itkonen et al, showed that UDP-GlcNAc is activated in PC-3 prostate cancer cells and can act as a modulator of prostate cancer growth, which reinforces the notion that these often overlooked protein modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer [37]. Finally, our results agree with those, recently reported, suggesting the beneficial effects of oleuropein against cancer, ageing, neurodegeneration, diabetes and diseases implying autophagy dysfunction [38,39]. Further understanding of the molecular mechanisms which are activated in response to different stimuli is therefore important towards the pharmaceutical development of novel treatment methods for prostate cancer.…”

Section: Discussionsupporting

confidence: 92%

Oleuropein is a Powerful Sensitizer of Doxorubicin-mediated Killing of Prostate Cancer Cells and Exerts Its Action via Induction of Autophagy

Papachristodoulou¹,

Tsoukala²,

Benaki³

et al. 2018

JCRT

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The phenolic component Oleuropein (OLEU), a bioactive natural product, has recently shown antiproliferative properties. Doxorubicin (DXR) is an anthracycline present in many chemotherapeutic schemes, although limited due to its cardio-toxic effects. Important research effort has been devoted therefore, to reducing DXR toxicity without compromising its antitumor efficacy. The anticancer actions of DXR and OLEU were assessed, on PC-3 prostate cancer cells, while cell cycle distribution and rate of apoptosis were assessed by flow cytometry. The autophagic process was determined via immunoblotting and immunofluorescent staining. Finally, cell extracts were analyzed by NMR spectroscopy. The present study showed that both DXR and OLEU inhibited PC-3 cells proliferation, while the co-treatment with DXR and OLEU resulted in an additive inhibition. Although the addition of OLEU to DXR did not alter significantly the cell cycle distribution, exhibited by each treatment alone, and produced a marginal increase on the rate of apoptosis, both compounds produced a remarkable induction of autophagy. In addition, treated cells exhibited significant metabolite alterations. This study demonstrates that OLEU, a basic component of the everyday diet, is capable of lowering significantly the cytotoxic dose of DXR, while obtaining an important anti-proliferative effect in prostate cancer cells.

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Section: Discussionsupporting

confidence: 92%

Oleuropein is a Powerful Sensitizer of Doxorubicin-mediated Killing of Prostate Cancer Cells and Exerts Its Action via Induction of Autophagy

Papachristodoulou¹,

Tsoukala²,

Benaki³

et al. 2018

JCRT

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“…The oleuropein doses used in the previous studies ranged from 2.5 mg/kg to 300 mg/kg . Even though there are limited studies regarding the effect of oleuropein in rats, all reported studies demonstrated beneficial effects of oleuropein in studied doses . Furthermore, there is no accepted therapeutic dose for oleuropein.…”

Section: Discussionmentioning

confidence: 99%

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

Taşkan

Yüce

Karataş

et al. 2019

J of Periodontal Research

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The Objective 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. Background Oleuropein is a flavonoid, which has potent anti‐inflammatory and bone‐protective effects. Methods 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 (12 mg/kg/day oleuropein, LDO group, n = 8); and periodontitis and high‐dose oleuropein group (24 mg/kg/day oleuropein, HDO group, n = 8). Periodontitis was induced via ligatures. Study period was 14 days, 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. Results Periodontitis group had highest alveolar bone loss, and these levels significantly decreased in LDO and HDO groups. Both 12 and 24 mg/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. Conclusion Oleuropein successfully decreased alveolar bone loss as a result of decreased osteoclastic activity, inflammation, and apoptosis and increased osteoblastic activity.

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“…Taken together, these findings fill a gap, considering that data on the dose‐dependence of the healthy effects of olive polyphenols are not available, in spite of the interest of the issue taking into account the reduced bioavailability of these molecules once given orally. The only data refer to protection against cisplatin‐induced acute renal injury in mice and to the dose‐dependent suppression of intracellular triglyceride accumulation in 3 T3 pre‐adipocytes during differentiation to adipocytes whereas no data are available on neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology

Pantano

Luccarini

Nardiello

et al. 2016

Brit J Clinical Pharma

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AIMIn TgCRND8 (Tg) mice we checked the dose-response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg kg À1 of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg kg À1 of diet) previously investigated. METHODSFour month-old Tg mice were equally divided into four groups and treated for 8 weeks with a modified low fat (5.0%) AIN-76 A diet (10 g day À1 per mouse) as such, supplemented with OLE (12.5 or 0.5 mg kg À1 of diet) or with a mix of polyphenols (50 mg kg À1 of diet) found in olive mill waste water. Behavioural performance was evaluated by the step down inhibitory avoidance and object recognition tests. Neuropathology was analyzed by immunohistochemistry. RESULTSOLE supplementation at 12.5 mg kg À1 of diet and the mix of polyphenols was found to improve significantly cognitive functions of Tg mice (P < 0.0001). Aß42 and pE-3Aß plaque area and number were significantly reduced in the cortex by OLE and in the cortex and hippocampus by the mix of polyphenols (P < 0.01, P < 0.001 and P < 0.0001). Similar autophagy induction was found in the brain cortex of differently treated mice. CONCLUSIONOur results extend previous data showing that the effects of OLE on behavioural performance and neuropathology are dosedependent and not closely related to OLE by itself. In fact, diet supplementation with the same dose of a mix of polyphenols found in olive mill waste water resulted in comparable neuroprotection.

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Oral administration of oleuropein attenuates cisplatin‐induced acute renal injury in mice through inhibition of ERK signaling

Abstract: The results of the current study suggest that oleuropein attenuated CP-induced acute renal injury, which was mediated through the inhibition of ERK signaling.

Cited by 56 publications

References 50 publications

Oleuropein is a Powerful Sensitizer of Doxorubicin-mediated Killing of Prostate Cancer Cells and Exerts Its Action via Induction of Autophagy

Oleuropein is a Powerful Sensitizer of Doxorubicin-mediated Killing of Prostate Cancer Cells and Exerts Its Action via Induction of Autophagy

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

Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology

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