In vitro and in vivo analysis of the antithrombotic and toxicological profile of new antiplatelets N-acylhydrazone derivatives and development of nanosystems

Sathler, P.C; Lourenço, André Luiz; Rodrigues, Carlos Rangel; Silva, Luiz Cláudio Rodrigues Pereira da; Cabral, Lúcio Mendes; Jordão, Alessandro K.; Cunha, Anna C.; Vieira, Maria Cecília Bastos; Ferreira, Vı́tor F.; Carvalho-Pinto, Carla Eponina; Kang, Hye Chung; Castro, Helena C.

doi:10.1016/j.thromres.2014.05.009

Cited by 32 publications

(18 citation statements)

References 56 publications

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“…Results showed cynatratoside-C at a concentration of 1000 mg l −1 induced only 5% RBC hemolysis. Hemolysis <10% indicates good hemocompatibility and non-toxicity with respect to erythrocyte membranes (Sathler et al 2014). The results of this study demonstrated that cynatratoside-C shows no cytotoxicity toward RBCs.…”

Section: Discussionmentioning

confidence: 59%

Cynatratoside-C efficacy against theronts of Ichthyophthirius multifiliis, and toxicity tests on grass carp and mammal blood cells

Fu¹,

Zhang²,

Xu³

et al. 2015

Dis. Aquat. Org.

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Infection by Ichthyophthirius multifiliis, a ciliated protozoan parasite, results in high fish mortality and causes severe economic losses in aquaculture. To find new, efficient anti-I. multifiliis agents, cynatratoside-C was isolated from Cynanchum atratum by bioassay-guided fractionation in a previous study. The present study investigated the anti-theront activity, determined the toxicity of cynatratoside-C to grass carp Ctenopharyngodon idellus and mammalian blood cells, and evaluated the protection of cynatratoside-C against I. multifiliis theront infection in grass carp. Results showed that all theronts were killed by 0.25 mg l −1 of cynatratoside-C in 186.7 ± 5.8 min. Cynatratoside-C at 0.25 mg l −1 was effective in treating infected grass carp and protecting naive fish from I. multifiliis infestation. The 96 h median lethal concentration (LC 50 ) of cynatratoside-C to grass carp and 4 h median effective concentration (EC 50 ) of cynatratoside-C to theront were 46.8 and 0.088 mg l −1 , respectively. In addition, the hemolysis assay demonstrated that cynatratoside-C had no cytotoxicity to rabbit red blood cells. Therefore, cynatratoside-C could be a safe and effective potential parasiticide for controlling I. multifiliis.

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Section: Discussionmentioning

confidence: 59%

Cynatratoside-C efficacy against theronts of Ichthyophthirius multifiliis, and toxicity tests on grass carp and mammal blood cells

Fu¹,

Zhang²,

Xu³

et al. 2015

Dis. Aquat. Org.

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“…Washed platelets were prepared as described elsewhere 42 . Briefly, blood was collected from healthy donors using a BD Vacutainer Safety-Lok blood collection set with a 23-gauge needle.…”

Section: Methodsmentioning

confidence: 99%

Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography

et al. 2015

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Functional imaging of proteolytic activity is an emerging strategy to quantify disease and response to therapy at the molecular level. We present a new peptide-based imaging probe technology that advances these goals by exploiting enzymatic activity to deposit probes labelled with near-infrared (NIR) fluorophores or radioisotopes in cell membranes of disease-associated proteolysis. This strategy allows for non-invasive detection of protease activity in vivo and ex vivo by tracking deposited probes in tissues. We demonstrate non-invasive detection of thrombin generation in a murine model of pulmonary embolism using our protease-activated peptide probes in microscopic clots within the lungs with NIR fluorescence optical imaging and positron-emission tomography. Thrombin activity is imaged deep in tissue and tracked predominantly to platelets within the lumen of blood vessels. The modular design of our probes allows for facile investigation of other proteases, and their contributions to disease by tailoring the protease activation and cell-binding elements.

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“…The body weight of these animals was determined, and, after 1-h fasting, compounds were administered orally. One hour postadministration, we anaesthetized the animals with a solution of ketamine and xylazine (100 and 16 mg/ kg, respectively), as proposed by Sathler and co-workers (Sathler et al 2014). Animals were placed in a supine position to continuously verify the possible lethality or cessation of anaesthesia during the experiment (30 min).…”

Section: Ethical Approvalmentioning

confidence: 99%

New approaches in tail‐bleeding assay in mice: improving an important method for designing new anti‐thrombotic agents

Saito

Lourenço

Kang

et al. 2016

Int J Experimental Path

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This report describes a modified, simple, low-cost and more sensitive method to determine bleeding patterns and haemoglobin concentration in a tail-bleeding assay using BALB/c mice and tail tip amputation. The cut tail was immersed in Drabkin's reagent to promote erythrocyte lysis and haemoglobin release, which was monitored over 30 min. The operator was blinded to individual conditions of the mice, which were treated with either saline (NaCl 0.15m), DMSO (0.5%) or clinical anti-thrombotic drugs. Our experimental protocols showed good reproducibility and repeatability of results when using Drabkin's reagent than water. Thus, the use of Drabkin's reagent offered a simple and low-cost method to observe and quantify the bleeding and rebleeding episodes. We also observed the bleeding pattern and total haemoglobin loss using untreated animals or those under anti-coagulant therapy in order to validate the new Drabkin method and thus confirm that it is a useful protocol to quantify haemoglobin concentrations in tail-bleeding assay. This modified method provided a more accurate results for bleeding patterns in mice and for identifying new anti-thrombotic drugs.

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In vitro and in vivo analysis of the antithrombotic and toxicological profile of new antiplatelets N-acylhydrazone derivatives and development of nanosystems

Cited by 32 publications

References 56 publications

Cynatratoside-C efficacy against theronts of Ichthyophthirius multifiliis, and toxicity tests on grass carp and mammal blood cells

Cynatratoside-C efficacy against theronts of Ichthyophthirius multifiliis, and toxicity tests on grass carp and mammal blood cells

Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography

New approaches in tail‐bleeding assay in mice: improving an important method for designing new anti‐thrombotic agents

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