Hydroxytyrosol inhibits phosphatidylserine exposure and suicidal death induced by mercury in human erythrocytes: Possible involvement of the glutathione pathway

Officioso, Arbace; Alzoubi, Kousi; Läng, Florian; Manna, Caterina

doi:10.1016/j.fct.2016.01.003

Cited by 55 publications

(40 citation statements)

References 55 publications

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“…To the extent that stimulated eryptosis may lead to anemia and thrombosis, it may be desirable to inhibit eryptosis. As a matter of fact, a wide variety of compounds such as blebbistatin, phlorhizin, vitamin C, resveratrol, reversine, hydroxytyrosol, volasertib, ASP3026 and teriflunomide have previously been shown to inhibit eryptosis in vitro . Some of these substances have previously been shown to counteract oxidative stress and may potentially be effective in vivo and could, therefore, be considered for the treatment of eryptosis‐induced anemia in different clinical conditions.…”

Section: Pharmacological Inhibition Of Oxidative Stress In Erythrocytmentioning

confidence: 99%

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

et al. 2018

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The average lifespan of circulating erythrocytes usually exceeds hundred days. Prior to that, however, erythrocytes may be exposed to oxidative stress in the circulation which could cause injury and trigger their suicidal death or eryptosis. Oxidative stress activates Ca -permeable nonselective cation channels in the cell membrane, thus, stimulating Ca entry and subsequent cell membrane scrambling resulting in phosphatidylserine exposure and activation of Ca -sensitive K channels leading to K exit, hyperpolarization, Cl exit, and ultimately cell shrinkage due to loss of KCl and osmotically driven water. While the mechanistic link between oxidative stress and anemia remains ill-defined, several diseases such as diabetes, hepatic failure, malignancy, chronic kidney disease and inflammation have been identified to display both increased oxidative stress as well as eryptosis. Recent compelling evidence suggests that oxidative stress is an important perpetrator in accelerating erythrocyte loss in different systemic conditions and an underlying mechanism for anemia associated with these pathological states. In the present review, we discuss the role of oxidative stress in reducing erythrocyte survival and provide novel insights into the possible use of antioxidants as putative antieryptotic and antianemic agents in a variety of systemic diseases.

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Section: Pharmacological Inhibition Of Oxidative Stress In Erythrocytmentioning

confidence: 99%

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

et al. 2018

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“…Signaling contributing to stimulation of eryptosis includes activated caspases, stimulated activity of casein kinase 1 α , Janus‐activated kinase JAK3, protein kinase C, and p38 kinase, as well as impaired activity of AMP activated kinase AMPK, cGMP‐dependent protein kinase, mitogen‐activated kinase and stress‐activated kinase MSK, PAK2 kinase, and sorafenib/sunitinib sensitive kinases . Eryptosis is triggered by a wide variety of xenobiotics and enhanced eryptosis is observed in several clinical conditions including dehydration, hyperphosphatemia, chronic kidney disease (CKD), hemolytic‐uremic syndrome, diabetes, hepatic failure, malignancy, sepsis, sickle‐cell disease, beta‐thalassemia, Hb‐C and G6PD‐deficiency, as well as Wilsons disease …”

Section: Introductionmentioning

confidence: 99%

Ceranib‐2‐induced suicidal erythrocyte death

Signoretto

Zierle

Bhuyan

et al. 2016

Cell Biochemistry & Function

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Ceramide is known to trigger apoptosis of nucleated cells and eryptosis of erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Besides ceramide, stimulators of eryptosis include increase of cytosolic Ca(2+) -activity ([Ca(2+) ]i ) and oxidative stress. Ceramide is degraded by acid ceramidase and inhibition of the enzyme similarly triggers apoptosis. The present study explored, whether ceramidase inhibitor Ceranib-2 induces eryptosis. Flow cytometry was employed to quantify phosphatidylserine-exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca(2+) ]i from Fluo3-fluorescence, reactive oxygen species (ROS) from DCF dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was estimated from hemoglobin concentration in the supernatant. A 48 h exposure of human erythrocytes to Ceranib-2 significantly increased the percentage of annexin-V-binding cells (≥50 μM) and the percentage of hemolytic cells (≥10 μM) without significantly modifying forward scatter. Ceranib-2 significantly increased Fluo3-fluorescence, DCF fluorescence and ceramide abundance. The effect of Ceranib-2 on annexin-V-binding was not significantly blunted by removal of extracellular Ca(2+) . Ceranib-2 triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to increase of ceramide abundance and induction of oxidative stress, but not dependent on Ca(2+) entry. Copyright © 2016 John Wiley & Sons, Ltd.

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“…Finally, HT ameliorates acrolein-induced cytotoxicity in retinal pigment epithelial cells, showing a protection from oxidative damage and mitochondrial dysfunction [78] and reduces acrylamideinduced cytotoxicity, preventing DNA damage and intracellular ROS formation in HepG2 cells [79]. In the last few years, several papers report data indicating that this dietary component is able to counteract the toxic effects linked to exposure of heavy metals, including Hg [80][81][82].…”

Section: Olive Oil Hydroxytyrosol In the Prevention Of Hg Toxicitymentioning

confidence: 99%

“…These biochemical alterations result in RBC morphological changes, associated with a reorganization of the cellular membrane, in which exposure of PS on the cell surface is the major event [37]. Experimental evidence of the efficacy of HT in preventing eryptosis in human RBC exposed in vitro to HgCl 2 treatment has been recently published by our group [81]. Cell conditioning with HT micro-molar concentrations prior to exposure to Hg causes a decrease in PS-exposing RBC, along with the restoration of ATP and GSH cellular content ( Figure 6).…”

Section: Ht Prevents Hg-induced Programmed Cell Death (Eryptosis) In mentioning

confidence: 99%

Nutritional Aspects of Food Toxicology: Mercury Toxicity and Protective Effects of Olive Oil Hydroxytyrosol

Officioso¹,

Tortora²

2016

J Nutr Food Sci

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Mercury represents one of the main environmental pollutants and human exposure to this heavy metal occurs primarily through nutritional sources, including contaminated fish. This highly toxic compound is known to pose serious threats to human health, including neurological alterations. Moreover, based on its effects on cardiovascular health, mercury exposure is now considered an independent risk factor for cardiovascular diseases. The possibility of reducing heavy metal toxicity through diet has attracted the interest of those responsible for the public health service. In this respect, the use of phytochemicals able to significantly counteract oxidative alterations as an attractive tool for the reduction of mercury toxicity has been proposed. Here we review recent evidence supporting the beneficial role of olive oil hydroxytyrosol in preventing mercury-induced alterations in both human erythrocytes and neuroblastoma cells. This novel biological effect exerted by hydroxytyrosol represents an additional mechanism responsible for the much-claimed health benefits of this dietary phenol. Taken together the reported findings encourage the use of virgin olive oil, characterized by a high hydroxytyrosol content, as an innovative approach in designing combined dietary and/or nutraceutical strategies to contrast mercury toxicity in humans.

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Hydroxytyrosol inhibits phosphatidylserine exposure and suicidal death induced by mercury in human erythrocytes: Possible involvement of the glutathione pathway

Cited by 55 publications

References 55 publications

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

Ceranib‐2‐induced suicidal erythrocyte death

Nutritional Aspects of Food Toxicology: Mercury Toxicity and Protective Effects of Olive Oil Hydroxytyrosol

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