Niacin-induced “Flush” Involves Release of Prostaglandin D<sub>2</sub>from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Papaliodis, Dean; Boucher, William; Kempuraj, Duraisamy; Michaelian, Margaret; Wolfberg, Adams; House, Michael; Theoharides, Theoharis C.

doi:10.1124/jpet.108.141333

Cited by 41 publications

(34 citation statements)

References 40 publications

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“…In mammalian organs, large amounts of PGD 2 are found only in the brain and in MC. Previous studies found MC-produced PGD 2 is the primary mediator of vasodilatation (the "niacin flush") after ingestion of niacin (nicotinic acid) [41]. Previously reported data reveals that non-IgE induced PGD 2 production was attenuated when ROS production was reduced (REF in comment).…”

Section: Discussionmentioning

confidence: 97%

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Dellinger¹,

Brooks

Plunkett

et al. 2012

J Nanomedic Nanotechnol

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Mast cells (MC) and peripheral blood basophils (PBB) are well known for their role in the allergic response mediated through high affinity IgE receptors (FcεRI). However, these cells can also be stimulated by other non-allergic secretagogues to release their inflammatory mediators. Certain fullerene derivatives (FD) have already been shown to stabilize FcεRI-mediated MC/PBB responses, but it is not know if they also stabilize these cells through non-IgEmediated mechanisms. A panel of FD was synthesized and tested for their ability to inhibit non-FcεRI mediated release from human MC and PBB. It was found that specifically engineered FD could significantly inhibit calcium ionophore, compound 48/80, somatostatin, and poly L-lysine induced MC degranulation and cytokine production, as well as blunt degranulation and cytokine production from N-formyl-methionine-leucine-phenylalanine (fMLP), poly L-lysine, and calcium ionophore stimulated PBB. The mechanism of inhibition was due in part to the prevention of secretagogueinduced increases in cellular reactive oxygen species (ROS) and calcium levels as well as the reduced activation of the MAPK signaling intermediates ERK1/ERK2 and LAT. Additionally, preincubation of MC with FD blunted the prostaglandin D 2 (PGD 2 ) production upon exposure to inflammatory stimuli. In both cell types, the extent of inhibition of mediator release in response to each secretagogue was dependent on the moieties/side chains attached to the carbon cage. These results further extend the utility of fullerene nanomaterials to control mediator release through non-IgE mediated pathways in MC/PBB.

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Section: Discussionmentioning

confidence: 97%

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Dellinger¹,

Brooks

Plunkett

et al. 2012

J Nanomedic Nanotechnol

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“…We recently showed that niacin induces serotonin release from platelets in a rat model (23). Serotonin has superficial vasodilatory actions (24), and elevated plasma serotonin levels (25) are associated with the facial flush characteristic of the Carcinoid syndrome (26).…”

Section: Discussionmentioning

confidence: 99%

A Quercetin Containing Supplement Reduces Niacin-Induced Flush in Humans

Kalogeromitros

Makris

Chliva

et al. 2008

Int J Immunopathol Pharmacol

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Coronary artery disease is associated with increased serum levels of cholesterol, triglycerides and LDL, but low levels of HDL. The most potent agent capable of reversing this trend is the vitamin nicotinic acid (niacin). However, compliance even with extended-release preparations and addition of acetylsalicylic acid (ASA) is hampered by the development of a feeling of erythema and burning ("flush"), especially on the face. We recently showed that the natural flavonoids quercetin and luteolin can eliminate "flush", as well as inhibit both niacin-induced plasma prostaglandin D, (PGD z ) and serotonin increase in an animal model. We conducted a pilot clinical study in humans. Four normal male subjects received (a) 1 g immediate release niacin either alone or after (b) the dietary formulation (Algonot-plus") containing 150 mg quercetin per capsule. Subjects completed a visual scale (l=no, 5=worst response) symptom assessment. Erythema and burning sensation scores were both 4.75±0.50 and lasted for 3.63±1.11 hours. After Algonot-plus" administration, both scores were reduced to 2.5±0.58 and lasted for only 1.68±O.70 hours. Quercetin also inhibited methylnicotinate-induced human mast cell PGD z release. These preliminary results suggest that quercetin could reduce niacin-induced "flush" in humans.Ingestion of the B 3-vitamin niacin (nicotinic acid) has been repeatedly shown to improve hypercholesterolemia and other lipoprotein abnormalities, while it also-increases HOL levels (1). Moreover, the combination of niacin with lovastatin has been shown to be superior to either agent alone (2-4). However, a serious limiting adverse effect is the development of significant facial erythema and warmth, known as "flush" that is more intense with immediate release than with extended release niacin (2, 5-6). Moreover, most of the over-the-counter formulations either do not contain sufficient niacin to have any effect or contain niacin metabolites that are ineffective (7).Niacin is thought to induce flush by stimulating the release of prostaglandin 02 (PG0 2) from the skin (8-9), most likely from dermal macrophages (10). However, co-administration of acetylsalicylic acid (ASA) does not reduce PGD 2 levels more than about 30% (II). Other measures used to reduce flush have included avoidance of alcohol and spicy foods with little benefit (12).We recently used a rat model of flush (13) and showed that niacin-induced skin vasodilation was accompanied by increased plasma PGD 2 , but also serotonin increases, both of which were inhibited along with the flush by the f1avonoids quercetin and luteolin (14). We therefore conducted a pilot clinical trial to investigate if a quercetin containing dietary supplement could inhibit niacin-induced flush in humans. MATERIALS AND METHODS MaterialsImmediate release macin caplets (250 mg each, SLO-NIACIN

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“…Classical vasodilatory mediators, such as histamine, bradykinin, serotonin, and acetylcholine do undergo changes in their skin transudate levels after niacin challenge (Morrow et al, 1992;Plummer et al, 1977). However, Papaliodis et al (2008) showed that niacin induced the release of serotonin from human platelets in vitro and elevated blood levels of serotonin after intraperitoneal injection of niacin in rats. Although further study will be needed to clarify the possible role of serotonin, the vast majority of evidence points to a strongly predominant role of AA metabolites as primary mediators of the flush response to niacin.…”

Section: Mediation Of Niacin Flush By Aa Metabolitesmentioning

confidence: 99%

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Messamore

Yao

2015

OCL

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-This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling.Keywords: Phospholipids / arachidonic acid / eicosanoids / niacin-induced flushing, endophenotype marker / schizophrenia Résumé -Signalisation des phospholipides, de l'arachidonate et de l'écosanoïde dans la schizophrénie. Cet article examine le rôle potentiel de l'acide arachidonique dans la physiopathologie de la schizophrénie. Il est discuté comment des niveaux anormaux d'acide arachidonique peuvent survenir, et comment la dérégulation des molécules de signalisation qui en découle est capable de perturber non seulement la signalisation de la dopamine, mais aussi de nombreux autres processus physiologiques associés avec cette maladie. Des doses pharmacologiques de niacine stimulent la libération d'acide arachidonique ; des molécules dérivées de l'acide arachidonique dilatent à leur tour les vaisseaux sanguins dans la peau. Une brusque rougeur de la peau en réponse à la niacine est observée de manière constante parmi les patients atteints de schizophrénie. La réponse anormale à la niacine peut donc servir de biomarqueur afin d'identifier un sous-type physiologique de la schizophrénie, associé à un système défectueux de signalisation des dérivés de l'acide arachidonique.

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Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Cited by 41 publications

References 40 publications

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

A Quercetin Containing Supplement Reduces Niacin-Induced Flush in Humans

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

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Niacin-induced “Flush” Involves Release of Prostaglandin D2from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Cited by 41 publications

References 40 publications

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

A Quercetin Containing Supplement Reduces Niacin-Induced Flush in Humans

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Contact Info

Product

Resources

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Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model