The Potent Inhibition of Vapiprost, a Novel Thromboxane A2 Receptor Antagonist, on the Secondary Aggregation and ATP Release of Human Platelets.

Horie, Shuichi; Yamada, Mayumi; Satoh, Megumi; Noritake, Shinobu; Hiraishi, Sayuri; Kizaki, Keiichiro; Kurusu, Osamu; Nakahara, Takeshi; Ishii, Hidemi; Kazama, Mutsuyoshi

doi:10.1248/bpb.20.625

Cited by 5 publications

(2 citation statements)

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“…At equimolar concentrations of ASA, the aminobenzopyranopyrimidine derivatives partially inhibited ADP-induced platelet aggregation in vitro, with pyrrolidino 3d and piperidino 3e derivatives significantly surpassing the antiaggregatory activity detected with the conventional antithrombotic drug in this experimental model. ASA has proved to possess a minor antiplatelet activity, against ADP aggregation in in vitro with respect to ex vivo tests [27], therefore the antiplatelet activity detected here for the aminobenzopyranopyrimidine derivatives will be substantiated by additional experiments performed on ex vivo platelet aggregation in guinea-pigs. The antiplatelet activity of the new derivatives could also contribute to the observed gastroprotection through the maintainance of an adequate gastric mucosal blood flow, considering that the involvement of platelet aggregation in ethanol-induced rat gastric mucosal injury has recently been hypothesized [28].…”

Section: Discussionmentioning

confidence: 65%

Synthesis and Pharmacological Screening of Novel Non-acidic Gastroprotective Antipyretic Anti-inflammatory Agents with Anti-platelet Properties

Bruno¹,

Schenone²,

Ranise³

et al. 2011

Arzneimittelforschung

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The preparation and screening of antipyretic, anti-inflammatory, analgesic, gastroprotective and antiplatelet activities of original non-acidic aminobenzo-pyranopyrimidine derivatives are described. Major and dose-dependent analgesic and antipyretic properties were detected in all the compounds after oral administration (6.25-100 mg kg-1) in the mouse writhing test and in the E. coli lipopolysaccharide-induced fever in the rat, respectively. Unlike the reference drug indometacin (ED50 ulcer = 9.1 mg kg-1), no gastrolesivity was displayed by all the new compounds up to 150 mg kg-1 so that therapeutical indices equal or higher than that of indometacin were calculated. Furthermore, at 100 mg kg-1 they were able to prevent ethanol-induced gastric mucosal injury in rats. At a 1 mmol/l concentration the compounds under study were as effective as acetylsalicylic acid in inhibiting in vitro platelet aggregation induced by adenosine diphosphate.

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Section: Discussionmentioning

confidence: 65%

Synthesis and Pharmacological Screening of Novel Non-acidic Gastroprotective Antipyretic Anti-inflammatory Agents with Anti-platelet Properties

Bruno¹,

Schenone²,

Ranise³

et al. 2011

Arzneimittelforschung

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“…The ATP released from platelets is measurable ex vivo with a lumi-meter in the presence of luciferin and magnesium in human samples (Horie et al, 1997) and in canine samples (Soloviev et al, 1999). As an alternative method, a release of 14 C-5HT into extracellular fluid can be detected by radioactivity, using platelets that incorporated 14 C-5HT into dense body during incubation at 37°C (Inagaki et al, 1984).…”

Section: Release Reactionsmentioning

confidence: 99%

Blood Coagulation Tests in Toxicological Studies-Review of Methods and Their Significance for Drug Safety Assessment-

Kurata

Horii²

2004

J. Toxicol. Sci.

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In general toxicological studies, prothrombin time and activated partial thromboplastin time are routinely measured to assess blood coagulation. Special (problem-driven) tests for blood coagulation are of significance to detect abnormalities and investigate the mechanism of toxicity in detail. In this review, we compiled widely scattered information on blood coagulation testing from different fields in the biological area, and reviewed the methods available and their significance in toxicological studies. The relevant literature cited here reports large species differences in platelet aggregation, coagulation factors or fibrinolysis, and technical limitations. However, the following tests are basically applicable to laboratory animals; (1) assays for individual coagulation factors and protein induced by vitamin K absence or antagonists (PIVKA) to investigate coagulation factor abnormalities; (2) platelet aggregation-, platelet adhesion-, platelet release-tests and von Willebrand factor assay to screen and/or investigate platelet dysfunction; (3) fibrin/fibrinogen degradation products (FDP), D-dimer and thromboelastogram to detect fibrinolitic abnormalities, and assays for plasminogen, plasmin and their activator/inhibitor to investigate fibrinolysis in detail; and (4) bleeding-time to grossly evaluate blood coagulation capability in vivo. An appropriate battery of these tests provides significant information for risk assessment of drugs.

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Sumac liposomes/mesenchymal stem cells fight methotrexate‐induced nephrotoxicity in rats via regulating Nrf‐2/Keap‐1/HO‐1 and apoptotic signaling pathways

Zahran,

Mohyeldin,

Refaat

et al. 2024

Archiv der Pharmazie

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Methotrexate (MTX) is commonly employed in cancer treatment, but its clinical use is restricted due to the MTX‐associated renal injury. This study investigates the combined potential of Rhus coriaria (sumac) and bone marrow mesenchymal stem cells (BMMSCs) against MTX‐induced nephrotoxicity in rats. The high‐resolution‐liquid chromatography‐mass spectrometry (HR‐LC‐MS) of sumac extract tentatively identified 22 phytochemicals, mostly flavonoids, anthocyanins, and steroids. Preparation of sumac liposomes attained a suitable particle size of 3041.33 ± 339.42 nm, a polydispersity index of 0.208 ± 0.086, and an encapsulation efficiency of 84.92 ± 3.47%. Rat BMMSCs were injected into the tail vein of the experimental rats (0.5 × 106 cells, intravenous [iv]) of seven treated groups. The experimental design relies on either pre‐ or posttreatment of rats with intraperitoneal (IP) sumac liposomes (SL) (200 mg/kg, daily with a dose of MTX (300 µg/kg/14 days). The histopathological examination and serum analysis of creatinine and urea revealed good results, besides regulating levels of oxidative stress and inflammatory markers. Additionally, a significant decrease in the gene expression levels of B‐Cell Lymphoma 2 (Bcl‐2) and caspases‐3 and −9, a remarkable increase in the Bcl‐2 Associated X‐Protein (Bax), nuclear factor erythroid 2‐related factor 2 (Nrf2), and heme‐oxygenase 1 expression, and a downregulation of Kelch‐like ECH‐associated protein 1 (Keap1). Collectively, the coadministration of SL with BMMSCs might be a potent therapeutic strategy for attenuation of MTX‐induced renal damage. The network pharmacology analysis identified the involved key hub genes as KEAP1, Nrf2, HMOX1, mitogen‐activated protein kinase (MAPK1), nuclear factor‐kappa B (NF‐KB), interleukin‐1 beta (IL‐1B), and caspase‐3. The docking results revealed strong binding affinities of 7‐O‐methyl‐cyanidin‐3‐O‐(2″‐galloyl)‐galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac‐based phytoconstituents against MTX‐induced nephrotoxicity.

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The Potent Inhibition of Vapiprost, a Novel Thromboxane A2 Receptor Antagonist, on the Secondary Aggregation and ATP Release of Human Platelets.

Cited by 5 publications

References 0 publications

Synthesis and Pharmacological Screening of Novel Non-acidic Gastroprotective Antipyretic Anti-inflammatory Agents with Anti-platelet Properties

Synthesis and Pharmacological Screening of Novel Non-acidic Gastroprotective Antipyretic Anti-inflammatory Agents with Anti-platelet Properties

Blood Coagulation Tests in Toxicological Studies-Review of Methods and Their Significance for Drug Safety Assessment-

Sumac liposomes/mesenchymal stem cells fight methotrexate‐induced nephrotoxicity in rats via regulating Nrf‐2/Keap‐1/HO‐1 and apoptotic signaling pathways

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