Toxicity and Cellular Uptake of Gold Nanorods in Vascular Endothelium and Smooth Muscles of Isolated Rat Blood Vessel: Importance of Surface Modification

SummaryRidogrel (6.3 × 10−6 to 10−4 M) inhibited contractions of isolated rat caudal arteries and rabbit femoral arteries caused by U-46619. The slope of an Arunlakshana-Schild plot (pA2-value: 3.4 × 10−6 M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within}D min of incubation of the blood vessel with the compound and easily reversible. Ridogrel antagonised contractions of isolated rabbit femoral arteries caused by prostaglandin Fzo2α in the same concentration range. Ridogrel also inhibited contractions induced by aggregating rat platelets on isolated rat caudal arteries (itt the presence of ketanserin 4 × 10−7 M) and on isolated rabbit pulmonary and femoral arteries (in the absence of ketanserin). Ridogrel had no effect on Ca2+-induced contractions in depolarised isolated rabbit femoral arteries, and at 10−4 M antagonised serotonin-induced contractions in this blood vessel. Its effect on serotonin-induced contractions was statistically significant but very small on isolated rat caudal arteries. These observations indicate that ridogrel is an antagonist of prostaglandin endoperoxide/thromboxane A2 and prostaglandin F2α raCeptors on vascular smooth muscle.

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Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages

Particle and Fibre Toxicology ◽

10.1186/s12989-021-00415-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Masahide Inoue ◽

Koji Sakamoto ◽

Atsushi Suzuki ◽

Shinya Nakai ◽

Akira Ando ◽

...

Keyword(s):

Immune Response ◽

Surface Modification ◽

Lung Injury ◽

Cellular Uptake ◽

Intratracheal Instillation ◽

Chemical Properties ◽

Raw264.7 Cells ◽

Neutrophilic Infiltration ◽

Silica Nanomaterials ◽

Physico Chemical

Abstract Background As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties. Results We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 μm; 3 μm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 μm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH2) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH2 induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH2 was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs. Conclusions Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.

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Coronary vasodilation mediated by T cells expressing choline acetyltransferase

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00694.2020 ◽

2021 ◽

Vol 321 (5) ◽

pp. H933-H939

Author(s):

Adrian H. Chester ◽

Ann McCormack ◽

Edmund J. Miller ◽

Mohamed N. Ahmed ◽

Magdi H. Yacoub

Keyword(s):

T Cells ◽

Blood Flow ◽

Blood Vessel ◽

Coronary Blood Flow ◽

Choline Acetyltransferase ◽

Vascular Endothelium ◽

Coronary Circulation ◽

Direct Interaction ◽

Coronary Vasodilation ◽

Ischemic Events

This study shows ChAT-expressing T cells can induce vasodilation of the blood vessel in the coronary circulation and that this effect relies on a direct interaction between T cells and the coronary vascular endothelium. The study establishes a potential immunomodulatory role for T cells in the coronary circulation. The present findings offer an additional possibility that a deficiency of ChAT-expressing T cells could contribute to reduced coronary blood flow and ischemic events in the myocardium.

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Surface modification of RNA nanoparticles by ionic interaction for efficient cellular uptake

Journal of Industrial and Engineering Chemistry ◽

10.1016/j.jiec.2018.10.013 ◽

2019 ◽

Vol 70 ◽

pp. 87-93 ◽

Cited By ~ 2

Author(s):

Hyunsu Jeon ◽

Sangwoo Han ◽

Hyejin Kim ◽

Jong Bum Lee

Keyword(s):

Surface Modification ◽

Cellular Uptake ◽

Ionic Interaction

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LEUKOTRIENES INDUCE THE ACUTE RELEASE OF TISSUE-TYPE PLASMINOGEN ACTIVATOR FROM PERFUSED RAT BLOOD VESSEL WALLS

10.1055/s-0038-1644387 ◽

1987 ◽

Author(s):

N Tranquille ◽

J J Emeis

Keyword(s):

Blood Vessel ◽

Plasminogen Activator ◽

Prostaglandin E1 ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Type Plasminogen Activator ◽

Acute Increase ◽

Vessel Walls ◽

Isolated Rat

In a previous publication (Blood 66, 86, 1985) we suggested, on the basis of inhibitor experiments, that lipoxygenase metabolites might be involved in the release of tissue-type plasminogen activator (t-PA) from vessel walls. To test this suggestion, isolated rat hindlegs were freed of blood with Tyrode-BSA solution, and subsequently perfused with Tyrode-BSA containing various lipoxygenase metabolites. The perfusate was collected at timed intervals and assayed for t-PA activity by a spectrophoto-metric procedure. Of the compounds tested (see Table) 5-HETE did not induce PA release. However, leukotriene (LT) C4 and LTD4 dose-dependently (10-200 nM) induced the release of t-PA, which plateaued at 160 and 200 nM, respectively. Peak levels of t-PA activity were found at one minute, although the amount of t-PA released was less than that induced by PAF-acether. The PA activity released proved to be t-PA by functional and immunological criteria. Release of t-PA induced by LTC4 and LTD 4 was inhibited by the LT receptor antagonist FPL-55712 (10 μM).Prostaglandin E1 and E2, prostacyclin and ZK 36374 did not induce acute t-PA release at 0.1-2.8 μM concentrations in our model. LTC4 and LTD4 also induced an acute increase of t-PA activity in vivo in rats at a dosage of 2 μg/kg i.v.The data show that LTC4 and LTD4 can directly induce the acute release of t-PA, possibly by interacting with an endothelial LT receptor.

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Cellular Uptake and Cytotoxicity of Varying Aspect Ratios of Gold Nanorods in HeLa Cells

ACS Applied Bio Materials ◽

10.1021/acsabm.9b00986 ◽

2020 ◽

Vol 3 (3) ◽

pp. 1374-1384 ◽

Cited By ~ 1

Author(s):

Deshani Fernando ◽

Shoukath Sulthana ◽

Yolanda Vasquez

Keyword(s):

Cellular Uptake ◽

Gold Nanorods ◽

Hela Cells ◽

Aspect Ratios

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Measurement of hydroxyl radical in rat blood vessel by microbore liquid chromatography and electrochemical detection: an on-line microdialysis study

Journal of Chromatography B Biomedical Sciences and Applications ◽

10.1016/s0378-4347(99)00367-9 ◽

1999 ◽

Vol 734 (2) ◽

pp. 277-283 ◽

Cited By ~ 19

Author(s):

T.H. Tsai ◽

F.C. Cheng ◽

L.C. Hung ◽

C.F. Chen

Keyword(s):

Liquid Chromatography ◽

Blood Vessel ◽

Hydroxyl Radical ◽

Electrochemical Detection ◽

Rat Blood ◽

On Line ◽

Microdialysis Study ◽

Microbore Liquid Chromatography

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Three different vasoactive responses of rat tail artery to nicotine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y99-114 ◽

1999 ◽

Vol 78 (1) ◽

pp. 20-28

Author(s):

Rui Wang ◽

Zunzhe Wang

Keyword(s):

Smooth Muscles ◽

Rat Tail Artery ◽

Vascular Smooth Muscles ◽

Vascular Effects ◽

Tail Artery ◽

Complete Relaxation ◽

Underlying Mechanisms ◽

Channel Currents ◽

Rat Tail ◽

Isolated Rat

The vasoactive effects of nicotine on isolated rat tail artery tissues were studied. Nicotine transiently contracted rat tail artery tissues (EC50, 55.6 ± 2 µM) in an extracellular Ca2+ dependent and endothelium-independent fashion. The blockade of alpha1-adrenoceptors, but not alpha2-adrenoceptors or P2X purinoceptors, inhibited the nicotine-induced contraction by 38 ± 7% (p < 0.05). Nicotine (1 mM) depolarized membrane by 13 ± 3 mV, but did not affect L-type Ca2+ channel currents, of the isolated rat tail artery smooth muscle cells. The phenylephrine-precontracted tail artery tissues were relaxed by nicotine (EC50, 0.90 ± 0.31 mM), which was significantly inhibited after the blockade of nicotinic receptors. Simultaneous removal of phenylephrine and nicotine, after a complete relaxation of the phenylephrine-precontracted tail artery strips was achieved by nicotine at accumulated concentrations (>=10 mM), triggered a Ca2+-dependent rebound long-lasting vasoconstriction (n = 20). This rebound contraction was abolished in the absence of calcium or in the presence of tetracaine in the bath solution. Pretreatment of vascular tissues with a nicotinic receptor antagonist did not affect the nicotine-induced vasoconstriction or nicotine withdrawal induced rebound contraction. The elucidation of the triphasic vascular effects of nicotine and the underlying mechanisms is important for a better understanding of the complex vascular actions of nicotine.Key words: nicotine, smokeless tobacco, vascular smooth muscles, contraction, relaxation.

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Synthesis of Gold Nanoparticles Coated with pH-Responsive Polymers and Evaluation of the Cellular Uptake

MRS Proceedings ◽

10.1557/opl.2012.477 ◽

2012 ◽

Vol 1416 ◽

Author(s):

Takeo Ito ◽

Eriko Kusaka ◽

Yu Isobe ◽

Sei-ichi Nishimoto

Keyword(s):

Cellular Uptake ◽

Gold Nanorods ◽

Near Infrared ◽

A549 Cells ◽

Endocytic Pathway ◽

Human Lung Cancer ◽

Ph Responsive ◽

Absorption Bands ◽

Responsive Polymers ◽

Ph Responsive Polymers

ABSTRACTGold nanorods (AuNRs) show surface plasmon absorption bands in the near-infrared region. This characteristic property has stimulated utilization of gold nanorods as novel nanoprobes for noninvasive bioimaging, such as photoacoustic tomography. Herein, we discuss the synthesis of a series of gold nanorods coated with pH-responsive polymers to investigate the effect of the surface structure and zeta potential of nanoparticles on cellular uptake via a surface charge-mediated endocytic pathway. The surface of the gold nanorods was modified with polyethylene glycol (PEG@AuNR) and tertiary amine derivatives, specifically, diethylaminoethyl ester (1@AuNRs), its amide analog (2@AuNRs), and dimethylaminoethyl ester (3@AuNRs). It was found that the pH-sensitivity of1@AuNRs was relatively high and the surface was positively charged at lower pH. In contrast, the tertiary amino group of1@AuNRs was deprotonated to form an electrostatically neutral surface at higher pH. The pH-responsive gold nanorods were incubated with A549 cells (human lung cancer cells) to quantify the amount of cellular uptake using inductively coupled plasma mass spectrometry. The results indicate that1@AuNRs can be taken up efficiently in the cells, and thereafter, slowly flow out of the cells. Interestingly, only small amounts of the amide analog (2@AuNRs) were taken into the cells, suggesting minor structural changes may affect the interaction between the cell surface and AuNRs. This study highlights a potential application of pH-sensitive nanorods as a probe for bioimaging the acidic environment of tumors.

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