scholarly journals Vesicles Generated during Storage of Red Blood Cells Enhance the Generation of Radical Oxygen Speciesin Activated Neutrophils

2011 ◽  
Vol 11 ◽  
pp. 173-185 ◽  
Author(s):  
Herbert Jank ◽  
Ulrich Salzer
Keyword(s):  
Inhibitory Effect ◽  
Ros Generation ◽  
Oxygen Species ◽  
Neutrophilic Granulocytes ◽  
Radical Oxygen Species ◽  
Activated Neutrophils ◽  
Specific Accumulation ◽  
Shed Vesicles

Erythrocytes are known to shed vesiclesin vivo, under various conditionsin vitro, and, with impact for transfusion medicine, during storage of red blood cell concentrates (Vstovesicles). Vstovesicles of blood transfusions have been shown to deliver glycosylphosphatidylinositol-linked proteins to recipient erythrocytes, to display prothrombotic activity, and to have an inhibitory effect on macrophages. The interaction of Vstovesicles with and their effect on neutrophilic granulocytes has not yet been studied in detail. Fluorescentlylabeled Vstoand calcium-induced vesicles were preparedin order to study the uptake of labeled vesicular components by neutrophils as compared to the process of phagocytosis of zymosan using flow cytometry and confocal microscopy. The activating effect of Vstovesicles on neutrophils was addressed by a luminometric assay for stimulated radical oxygen species (ROS) generation. Coincubation of vesicles and neutrophils results in a transfer of vesicular components to the cells. This uptake is different from a phagocytotic process and is enhanced upon interference with the cellular actin cytoskeleton. Preincubation of neutrophils with Vstovesicles results in an enhanced ROS generation by neutrophils, which is further increased upon fMLP stimulation and during zymosan phagocytosis. The activating effect of Vstovesicles on neutrophils might be due to the specific accumulation of lysophospholipidsin Vstovesicles and should be considered as a possible contributor to the pathogenesis of transfusion-related acute lung injury.

scholarly journals Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

2022 ◽  
Vol 2022 ◽  
pp. 1-14
Author(s):  
Lu Zhou ◽  
Peng Yu ◽  
Ting-ting Wang ◽  
Yi-wei Du ◽  
Yang Chen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Inhibitory Effect ◽  
Ros Generation ◽  
Molecular Events ◽  
Mda Content ◽  
Effect Of Pd ◽  
In Cis

Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 μM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc− inhibitor erastin (10 μM), and the effect of the 40 μM dose of PD was more obvious than that of ferrostatin-1 (1 μM) and deferoxamine (DFO, 100 μM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc−-GSH-GPx4 axis and iron metabolism.

β-Adrenergic signaling stimulates osteoclastogenesis via reactive oxygen species

2013 ◽  
Vol 304 (5) ◽  
pp. E507-E515 ◽  
Author(s):  
Hisataka Kondo ◽  
Shoko Takeuchi ◽  
Akifumi Togari
Keyword(s):  
Reactive Oxygen Species ◽  
Raw 264.7 Cells ◽  
Ros Generation ◽  
Raw 264.7 ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Adrenergic Signaling ◽  
Intracellular Ros

Sympathetic signaling regulates bone resorption through receptor activator of nuclear factor-κB ligand (RANKL) expression via the β-adrenergic receptor (β-AR) on osteoblasts. Reactive oxygen species (ROS) are known as one type of osteoclast regulatory molecule. Here we show that an antioxidant, α-lipoic acid (α-LA), treatment prevent the β-adrenergic signaling-induced bone loss by suppressing osteoclastogenesis, and sympathetic signaling directly regulates osteoclastogenesis through β2-AR expressed on osteoclasts via intracellular ROS generation. In an in vitro study, the β-AR agonist isoprenaline increased intracellular ROS generation in osteoclasts prepared from bone marrow macrophages (BBMs) and RAW 264.7 cells. Isoprenaline enhanced osteoclastogenesis through β2-AR expressed on BMMs and RAW 264.7 cells. The antioxidant α-LA inhibited isoprenaline-enhanced osteoclastogenesis. Isoprenaline increased the expression of osteoclast-related genes such as nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1, tartrate-resistant acid phosphatase, and cathepsin K on osteoclasts. α-LA also inhibited isoprenaline-induced increases of these gene expressions. These in vitro results led to the hypothesis that β-adrenergic signaling directly stimulates osteoclastogenesis via ROS generation. In an in vivo study, isoprenaline treatment alone caused oxidative damage in local bone and reduced bone mass because of an increase in bone resorption, and, in α-LA-treated mice, isoprenaline did not increase tibial osteoclast number even though the RANKL-to-osteoprotegerin ratio increased. These in vitro and in vivo results indicate that β-adrenergic signaling, at least in part, directly stimulates osteoclastogenesis through β2-AR on osteoclasts via ROS generation.

The histone Deacetylase Inhibitor Givinostat in Combination with Sorafenib Induces Reactive Oxygen Species (ROS) Generation and Exerts Potent Antitumor Effects in NOD/SCID Mice with Hodgkin Lymphoma Cell Line Xenografts

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3711-3711
Author(s):  
Silvia L Locatelli ◽  
Anna Guidetti ◽  
Loredana Cleris ◽  
Silvia Tartari ◽  
Alessandro M. Gianni ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Drug Combination ◽  
Fold Increase ◽  
Time Dependent ◽  
Ros Generation ◽  
Oxygen Species ◽  
Sorafenib Treatment

Abstract Abstract 3711 INTRODUCTION: Patients with refractory or relapsed classical Hodgkin Lymphoma (cHL) represent an unmet medical need and would benefit from the development of new therapies. Histone deacetylases (HDACs) and the RAF/MEK/ERK pathway are aberrantly controlled in cHL and influence a broad repertoire of tumor processes, suggesting a rationale for therapeutically targeting these pathways. We targeted these pathways using the HDAC inhibitor Givinostat (Italfarmaco S.p.A., Milan, Italy), and the RAF/MEK/ERK inhibitor Sorafenib (Nexavar, Bayer, Germany, EU) in order to investigate in vitro and in vivo the activity and mechanism(s) of action of this two-drug combination. METHODS: Three cHL cell lines, including HDLM-2, L-540 and HD-MyZ, were used to investigate the effects of Givinostat and Sorafenib, used alone or in combination, by means of in vitro assays evaluating cell growth and cell survival. Additionally, live cell imaging was used to asses the production of reactive oxygen species (ROS), and Western blotting (WB) to assess modulating effects of the two-drug combination on MAPK, PI3K/AKT, HDACs as well as the apoptotic pathways. The efficacy of Givinostat/Sorafenib combination was finally confirmed in NOD/SCID mice with cHL cell line xenografts. RESULTS: While Givinostat and Sorafenib as single agents exerted a limited activity against cHL cells, the combined Givinostat/Sorafenib treatment was associated with potent dephosphorylation of MAPK and PI3K/Akt pathways and significantly increased H3 and H4 acetylation due to a nearly complete inhibition of class I and II HDACs. Furthermore, these events were associated with a time-dependent synergistic cell growth inhibition (70% to 90%) in all Givinostat/Sorafenib-treated cHL cells. Upon Givinostat/Sorafenib exposure, HDLM-2 and L-540 cell lines showed significantly (P ≤.0001) increased levels of apoptosis (90 ± 2% and 96 ± 1%, respectively) and mitochondrial dysfunction (up to 70%, P≤.0001), as compared with single agents. Apoptosis induced by Givinostat/Sorafenib combination failed to induce processing of caspase-8, −9, −3, or cleavage of PARP, and was not reversed by the pan-caspase inhibitor Z-VADfmk, suggesting the occurrence of caspase-independent apoptosis. Besides downregulating the expression of the anti-apoptotic protein Mcl-1 and ERK1/2 phosphorylation, Givinostat/Sorafenib strongly increased expression of the BH-3 only protein Bim, compared to single treatments. These findings were dependent on a potent, early and time-dependent ROS generation (up to 60%, P≤.0001) that was synergistically induced by Givinostat/Sorafenib treatment. Additionally, pretreatment of cHL cells with the ROS inhibitor YCG063 prevented the generation of ROS as well as mitochondrial membrane depolarization along with cell death induced by the two-drug combination, suggesting that ROS generation is the triggering event in Givinostat/Sorafenib induced-cell death. In vivo Givinostat/Sorafenib treatment significantly reduced the growth of L-540 and HD-MyZ nodules, resulting in an average 35% to 65% tumor growth inhibition (P ≤.0001) compared to single treatments, in the absence of any toxicity. Interestingly, as compared to controls or treatment with single agents, the combined Givinostat/Sorafenib treatment significantly increased in vivo Bim expression (7- to 21-fold increase, P ≤.0001), resulting in a marked tumor necrosis (3- to 5-fold increase, P ≤.0001). CONCLUSIONS: The combined Givinostat/Sorafenib treatment demonstrates a potent preclinical in vitro and in vivo activity against cHL cell lines by targeting aberrant expression of HDACs and MAPK. Antitumor activity of this combination involves ROS generation and Bim upregulation and provides a rationale for clinical studies using this combination in refractory/relapsed cHL patients. Disclosures: No relevant conflicts of interest to declare.

The PI3K/ERK Dual Inhibitor AEZS-136 Induces ROS-Dependent Necroptotic Cell Death and Exerts Potent Antitumor Effects In NOD/SCID Mice With Hodgkin Lymphoma Cell Line Xenografts

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3067-3067
Author(s):  
Silvia L Locatelli ◽  
Giuliano G Stirparo ◽  
Silvia Tartari ◽  
Elena Saba ◽  
Luca Rubino ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
S Phase ◽  
Scid Mice ◽  
Ros Generation ◽  
Oxygen Species ◽  
Dual Inhibitor ◽  
Dose Dependent

Abstract Introduction Disease relapse and resistance to chemotherapy represent challenging issues for Hodgkin Lymphoma (HL) patients. PI3K/AKT and RAF/MEK/ERK pathways are constitutively activated in the majority of HL patients, thus representing attractive therapeutic targets. Previous results from our phase II study indicate that combining the PI3K/AKT inhibitor perifosine with the RAF/MEK/ERK inhibitor sorafenib can achieve significant clinical responses in relapsed/refractory HL. The present study was therefore aimed at characterizing the in vitro and in vivo activity and mechanism(s) of action of a novel PI3K/ERK dual inhibitor AEZS-136 (Æterna Zentaris GmbH, Germany, EU). Methods Four HL cell lines (L-540, SUP-HD1, KM-H2 and L-428) were used to investigate the in vitro effects of AEZS-136 on cell growth, cell cycle distribution, gene expression profiling (GEP), and apoptosis. Live cell imaging experiments were performed to asses the production of reactive oxygen species (ROS). Western blotting (WB) was used to assess the effects of AEZS-136 on MAPK and PI3K/AKT pathways as well as apoptosis. The antitumor efficacy of AEZS-136 was investigated in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Results Exposure of L-540, SUP-HD1, KM-H2 and L-428 cell lines to AEZS-136 induced a marked, early and time-dependent dephosphorylation of PI3K/Akt and MAPK pathways that was associated with a significant time and dose-dependent cell growth inhibition [80 ± 3% (mean ±SEM) in the L-540 and SUP-HD1 responsive cell lines] and S phase cell cycle arrest. Indeed, upon AEZS-136 treatment the mean (±SEM) percentages of cells in S phase were reduced by 3-fold (13 ± 1%) as compared to control (33 ± 2%). Significant levels of cell death, as assessed by AnnexinV/PI staining, were only observed in L-540 (62 ± 9 vs 14 ± 3%, P ≤.0001) and SUP-HD1 (46 ± 2% vs 15 ± 2%, P ≤.0001) cell lines and were associated with severe mitochondrial dysfunction (up to 40%, P ≤.001). While no activation of caspase-3 and PARP cleavage were observed in L-540 and SUP-HD1 cells treated with AEZS-136, a potent generation of reactive oxygen species (ROS) was observed upon AEZS-136 treatment (up to 90%, P≤.0001). Pretreating cells with the ROS inhibitor YCG063 strongly inhibited AEZS-136-induced ROS generation, mitochondrial dysfunction and cell death, whereas the pan-caspase inhibitor Z-VADfmk did not. Since ROS generation has been implicated in mediating necroptosis, we tested if blocking programmed necrosis with Necrostatin-1 could prevent AEZS-136-induced cytotoxicity. When L-540 cells were treated with AEZS-136 in the presence of Necrostatin-1, cell death and ROS generation were completely prevented, suggesting that cell death was mechanistically related to necroptosis. Additionally, HL cells responsive to AEZS-136-induced cell death showed a pronounced JNK activation whose inhibition by the JNK inhibitor SP600125 reduced cell death and ROS generation. Furthermore, AEZS-136-increased JNK phosphorylation was inhibited by Necrostatin-1 or YCG063, suggesting that ROS-dependent necroptosis was linked to JNK. Interestingly, GEP analysis of L-540 and SUP-HD1 cell lines, but not KM-H2 and L-428 cells, indicated that AEZS-136 treatment induced upregulation of genes involved in positive regulation of cell death. In addition, in KM-H2 and L-428 cells, AEZS-136 strikingly induced the expression of the immediate early response 3 (IER3). Silencing of IER3 restored sensitivity of KM-H2 and L-428 cells to AEZS-136-induced necroptotic cell death, suggesting that IER3 acts as the signaling molecule that mediated AEZS-136-resistance to oxidative cell death. Finally, in vivo experiments were conducted to investigate the antitumor activity of AEZS-136. Treatment of NOD/SCID mice bearing L540 tumor nodules with increasing dose of AEZS-136 (30 – 60 mg/Kg body weight, PO, 5 days/2 weeks) resulted in a dose-dependent reduction of tumor growth (mean TGI of 70%, P ≤.0001) compared to vehicle-treated controls. No mice experienced any apparent treatment-related toxicity. Conclusions The PI3K/ERK dual inhibitor AEZS-136 demonstrates a potent antitumor activity against HL cell lines by targeting aberrant expression of MAPK and PI3K/Akt pathways. These data support further clinical evaluation of AEZS-136 in refractory/relapsed HL patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites

2013 ◽  
Vol 33 (1) ◽  
pp. 41-53 ◽  
Author(s):  
J J van Tonder ◽  
M Gulumian ◽  
A D Cromarty ◽  
V Steenkamp
Keyword(s):  
Apoptotic Cell ◽  
Ros Generation ◽  
Oxygen Species ◽  
Cellular Viability ◽  
Cytotoxic Effects ◽  
Hepatocyte Injury ◽  
Intracellular Changes ◽  
Vitro Effect

The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo. N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds. The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane. HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis. None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment. All three test compounds also induced apoptotic cell death, which was inhibited by NAC. Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations. As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity.

scholarly journals Melatonin Attenuates Oxidative Damage Induced by Acrylamide In Vitro and In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoqi Pan ◽  
Lanlan Zhu ◽  
Huiping Lu ◽  
Dun Wang ◽  
Qing Lu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Damage ◽  
Inhibitory Effect ◽  
Oxygen Species ◽  
Nuclear Condensation ◽  
Rat Cerebellum ◽  
Gait Abnormality ◽  
Neurotoxic Agent

Acrylamide (ACR) has been classified as a neurotoxic agent in animals and humans. Melatonin (MT) has been shown to be potentially effective in preventing oxidative stress related neurodegenerative disorders. In this study, whether MT exerted a protective effect against ACR-induced oxidative damage was investigated. Results in cells showed that reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after ACR treatment for 24 h. MT preconditioning or cotreatment with ACR reduced ROS and MDA products, whereas the inhibitory effect of MT on oxidant generation was attenuated by blocking the MT receptor. Increased DNA fragmentation caused by ACR was significantly decreased by MT coadministration. In vivo, rats at 40 mg/kg/day ACR by gavage for 12 days showed weight loss and gait abnormality, Purkinje cell nuclear condensation, and DNA damage in rat cerebellum. MT (i.p) cotreatment with ACR not only recovered weight and gait of rats, but also decreased nuclear condensation and DNA damage in rat cerebellum. Using MDA generation, glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in rat cerebellum as indicators, MT alleviated ACR-induced lipid peroxidation and depressed antioxidant capacity. Our results suggest that MT effectively prevents oxidative damage induced by ACR.

scholarly journals Ghrelin Ameliorates Diabetic Retinal Injury: Potential Therapeutic Avenues for Diabetic Retinopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jie Bai ◽  
Fan Yang ◽  
Ruiqi Wang ◽  
Qinghui Yan
Keyword(s):  
Reactive Oxygen Species ◽  
Diabetic Retinopathy ◽  
Cell Damage ◽  
Reactive Oxygen ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ros Generation ◽  
Oxygen Species

Ghrelin has anti-inflammatory, antioxidant, and antiapoptotic effects, and it may be beneficial for the treatment of many ophthalmic diseases, such as cataract, uveitis, and glaucoma. Our previous work proved that ghrelin pretreatment reduced the apoptosis of lens epithelial cells induced by hydrogen peroxide, reduced the accumulation of reactive oxygen species (ROS), and effectively maintained the transparency of lens tissue. However, no study has yet investigated the effect of ghrelin on retina. In this study, we conducted in vitro and in vivo experiments to explore the effect of ghrelin on high-glucose- (HG-) induced ARPE-19 cell damage and diabetic retinopathy in streptozotocin-induced diabetic rats. ARPE-19 cells were incubated in a normal or an HG (30 mM glucose) medium with or without ghrelin. Cell viability was measured by 3-(4, 5-dimethylthiazol-3-yl)-2,5-diphenyl tetrazolium bromide assay, and apoptosis was detected by the Hoechst–PI staining assay. Intracellular reactive oxygen species (ROS) production levels within cells were measured using 2 ′ ,7 ′ -dichlorofluorescein diacetate staining, and the contents of superoxide dismutase and malondialdehyde were measured using relevant detection kits. The expression levels of IL-1β and IL-18 were measured using an enzyme-linked immunosorbent assay, and those of NLRP3, IL-1β, and IL-18 were measured using Western blotting. The rat diabetes models were induced using a single intraperitoneal injection of streptozotocin (80 mg/kg). The morphological and histopathological changes in the retinal tissues were examined. The results indicated that ghrelin reduced ROS generation, inhibited cell apoptosis and the activation of NLRP3 inflammasome, inhibited the apoptosis of retinal cells in diabetic rats, and protected the retina against HG-induced dysfunction. In conclusion, ghrelin may play a role in the treatment of ocular diseases involving diabetic retinopathy.

scholarly journals Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis

2009 ◽  
Vol 297 (5) ◽  
pp. L846-L855 ◽  
Author(s):  
Shubha Murthy ◽  
Andrea Adamcakova-Dodd ◽  
Sarah S. Perry ◽  
Linda A. Tephly ◽  
Richard M. Keller ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Tnf Α

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-α and ROS in a Rac1-dependent manner. TNF-α was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro . More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

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