scholarly journals Importance of platelets in experimental venous thrombosis in the rat

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2281-2286 ◽  
Author(s):  
JM Herbert ◽  
A Bernat ◽  
JP Maffrand
Keyword(s):  
Venous Thrombosis ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Progressive Increase ◽  
High Dose ◽  
Experimental Conditions ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Tissue Thromboplastin ◽  
Dose Dependent

Abstract Venous thrombosis was induced by ligature of the inferior vena cava in rats whose blood was made hypercoagulable by intravenous (IV) administration of tissue thromboplastin. From a dose-response showing that the administration of increasing doses of tissue thromboplastin resulted in a subsequent progressive increase of thrombus weight, two concentrations of tissue thromboplastin were chosen: a high dose (550 microL/kg, IV) where thrombus formation was optimal and a concentration (7 microL/kg, IV) where tissue thromboplastin-hypercoagulability was intermediate. In both experimental conditions, leukopenia provoked by a myelotoxic drug did not influence the development of venous thrombosis. However, after thrombocytopenia induced by an antiplatelet antiserum, a dramatic decrease in thrombus formation was observed in animals that had been pre-challenged with the lower dose of tissue thromboplastin, whereas decrease in platelet count did not affect venous thrombosis under high thrombogenic challenge. When administered orally 2 hours before thrombosis induction, the ticlopidine analogue clopidogrel showed dose-dependent inhibition of thrombus formation in animals that were pre-challenged with a low dose of tissue thromboplastin (ED50 = 7.9 +/- 1.5 mg/kg, orally) but remained ineffective against high tissue thromboplastin-induced venous thrombosis. We further determined the effect of heparin and hirudin, and showed that both of these drugs exhibited a more potent antithrombotic activity after injection of the lower dose of tissue thromboplastin than after injection of a high dose of tissue thromboplastin. Therefore, using our model of stasis and hypercoagulability, platelet activation played a major role in the development of venous thrombosis when the thrombogenitic stimulus was mild.

scholarly journals Importance of platelets in experimental venous thrombosis in the rat

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2281-2286 ◽  
Author(s):  
JM Herbert ◽  
A Bernat ◽  
JP Maffrand
Keyword(s):  
Venous Thrombosis ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Progressive Increase ◽  
High Dose ◽  
Experimental Conditions ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Tissue Thromboplastin ◽  
Dose Dependent

Venous thrombosis was induced by ligature of the inferior vena cava in rats whose blood was made hypercoagulable by intravenous (IV) administration of tissue thromboplastin. From a dose-response showing that the administration of increasing doses of tissue thromboplastin resulted in a subsequent progressive increase of thrombus weight, two concentrations of tissue thromboplastin were chosen: a high dose (550 microL/kg, IV) where thrombus formation was optimal and a concentration (7 microL/kg, IV) where tissue thromboplastin-hypercoagulability was intermediate. In both experimental conditions, leukopenia provoked by a myelotoxic drug did not influence the development of venous thrombosis. However, after thrombocytopenia induced by an antiplatelet antiserum, a dramatic decrease in thrombus formation was observed in animals that had been pre-challenged with the lower dose of tissue thromboplastin, whereas decrease in platelet count did not affect venous thrombosis under high thrombogenic challenge. When administered orally 2 hours before thrombosis induction, the ticlopidine analogue clopidogrel showed dose-dependent inhibition of thrombus formation in animals that were pre-challenged with a low dose of tissue thromboplastin (ED50 = 7.9 +/- 1.5 mg/kg, orally) but remained ineffective against high tissue thromboplastin-induced venous thrombosis. We further determined the effect of heparin and hirudin, and showed that both of these drugs exhibited a more potent antithrombotic activity after injection of the lower dose of tissue thromboplastin than after injection of a high dose of tissue thromboplastin. Therefore, using our model of stasis and hypercoagulability, platelet activation played a major role in the development of venous thrombosis when the thrombogenitic stimulus was mild.

Effect of Various Antiplatelet Agents on Acute Arterial Thrombosis in the Rat

1993 ◽  
Vol 70 (05) ◽  
pp. 812-816 ◽  
Author(s):  
A Bernat ◽  
A M Mares ◽  
G Defreyn ◽  
J P Maffrand ◽  
J M Herbert
Keyword(s):  
Thrombus Formation ◽  
Platelet Activating Factor ◽  
Thromboxane A2 ◽  
Antiplatelet Agents ◽  
High Dose ◽  
Arterial Thrombus ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Thromboxane A2 Synthetase Inhibitor ◽  
Wall Injury

SummaryElectrical stimulation of the rat carotid artery causes a deep medial injury and the formation of a platelet-rich thrombus.Occlusive thrombosis at sites of vessel wall injury was significantly reduced after the oral administration of clopidogrel, a potent analogue of ticlopidine, which showed dose-dependent inhibition of the thrombus formation (ED50 = 1.0 ±0.2 mg/kg, p.o.). Accumulation of thrombotic material was also considerably reduced after the i. v. administration of SR 27417, a highly potent and selective platelet activating factor receptor antagonist (ED50 = μg/kg, i.v.), nafagrel, a thromboxane A2 synthetase inhibitor (ED50 = 1.3 mg/kg, i.v.) and hirudin (ED50 = 140 μg/ kg, i.v.). A high dose (20 mg/kg, i.v.) of the anti-adhesive tetrapeptide Arg-Gly-Asp-Ser (RGDS) showed only a slight effect on thrombus formation whereas aspirin was ineffective.These results confirm that ADP and thromboxane A2 play key roles in the initiation and progression of arterial thrombus formation and suggest that platelet activating factor may also modulate thrombosis in this experimental model.

scholarly journals Dose-Dependent Inhibition of Experimental Arterial Thrombosis by Carbenicillin and Ticarcillin

1977 ◽  
Author(s):  
B.T. Lyman ◽  
G.J. Johnson ◽  
J.G. White
Keyword(s):  
Arterial Thrombosis ◽  
Low Dose ◽  
Thrombosis Prophylaxis ◽  
High Dose ◽  
Antithrombotic Agents ◽  
Total Occlusion ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
High Doses ◽  
Dose Dependent

Drugs that inhibit platelet (PL) function may be useful in the prophylaxis of arterial thrombosis. We have shown that carbenicillin (CARB) and ticarcillin (TIC) cause dose-dependent inhibition of PL aggregation (AGG) in dogs, and that high doses of either of these penicillins significantly decrease the frequency of thrombosis in pronase (PN) injected arteries of dogs. Using this model we have compared the thrombosis prophylaxis effectiveness of these penicillins administered in low dose (250mg/Kg/24 hr, s.c.) (LD-P) versus high dose (750mg/Kg/24 hr, s.c.) (HD-P). Treatment for 3 to 7 days with LD-P resulted in marked inhibition of ADP-induced AGG, but had little or no effect on collagen-induced AGG, while HD-P routinely inhibited collagen as well as ADP-induced AGG. Control dogs were untreated, and their PL function remained normal. Thrombosis with total occlusion occurred in 13 of 15 arteries in control dogs, while only 3 of 29 segments totally occluded in HD-P treated dogs (χ2 = 21.7; p<0.001). However, total occlusion developed in 13 of 20 arteries in dogs receiving LD-P (χ2 = 1.1; p<0.3). The frequency of occlusion was significantly lower (p<0.001) following treatment with HD-P than LD-P. Aspirin (ASA) administration in low dose (650mg/24 hr p.o.) (LD-A) or high dose (2600mg/24 hr p.o.) (HD-A) uniformly inhibited collagen-induced PL AGG, but total occlusion developed in 11 of 16 PN injected arteries in dogs given LD-A, and in 10 of 12 arteries in dogs given HD-A. We conclude that CARB and TIC are effective experimental antithrombotic agents. Their effect is dose-dependent and closely correlated with inhibition of collagen-induced PL AGG. In high doses CARB and TIC are more effective than ASA in preventing PN induced arterial thrombosis. CARB and TIC warrant further study as potentially useful antithrombotic agents in humans.

Recombinant Full-length Tissue Factor Pathway Inhibitor (TFPI) Prevents Thrombus Formation and Rethrombosis after Lysis in a Rabbit Model of Jugular Vein Thrombosis

1996 ◽  
Vol 76 (04) ◽  
pp. 615-620 ◽  
Author(s):  
Brigitte Kaiser ◽  
Jawed Fareed
Keyword(s):  
Blood Flow ◽  
Vessel Wall ◽  
Tissue Factor Pathway Inhibitor ◽  
Jugular Vein ◽  
Thrombus Formation ◽  
Thrombotic Occlusion ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Tissue Factor Pathway ◽  
Dose Dependent

SummaryIn the jugular vein of rabbits thrombus formation was induced by vessel wall damage using a balloon catheter and following reduction of blood flow by 80-90% for 60 min (partial stasis). The blood flow in the vein was measured continuously and the incidence of primary thrombus formation, the time until lysis with recombinant tissue-type plasminogen activator (rt-PA) as well as the incidence of rethrombosis after lysis were determined. At the end of the experiment the wet weight of the thrombus formed inside the vessel was measured. For the determination of haemostaseological parameters blood was drawn from the cannulated femoral artery.Recombinant full-length tissue factor pathway inhibitor (TFPI) was studied with regard to its effect both on primary thrombus formation and on rethrombosis after lysis. In control animals damage of the vessel wall combined with partial stasis led to the formation of occlusive venous thrombi. In vitro bolus injection of TFPI (5,10,20 Μg/kg) at the time of thrombus induction prevented the formation of venous thrombi during the 1 h period of partial stasis. In the subsequent observation period a dose-dependent inhibition of later occurring partial or complete thrombotic occlusion was found. At the dose of 20 Μg/kg i.v. in all animals TFPI prevented a complete thrombotic occlusion of the vein up to 3 h after stasis. To study the effectiveness of TFPI on rethrombosis after lysis TFPI was injected i.v. after lysis of the thrombus with rt-PA (600 Μg/kg i.v. bolus + 600 Μg/kg i.v. infusion over 60 min). In saline treated control rabbits a reocclusion of the vessel was seen in 8 of 10 animals. TFPI (10, 20, 40 Μg/kg i.v.) injected at the end of rt-PA administration caused a dose-dependent inhibition of thrombotic reocclusion after lysis. At 40 Μg/kg i.v. the formation of occlusive thrombi was prevented up to 3 h after lysis. TFPI at the doses used caused modest anticoagulant effects in global clotting assays; activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were only slightly prolonged. A clear and dose-dependent prolongation of clotting times was only seen in the Heptest® assay.The results show that the physiologic coagulation inhibitor TFPI acts as a strong antithrombotic agent in an experimental model of venous thrombus formation and thrombotic reocclusion after lysis in rabbits.

Dose-Dependent Antithrombotic Effects of Apixaban, an Oral Direct Factor Xa Inhibitor, in Prevention and Treatment of Thrombosis in Rabbit Models of Arteriovenous-Shunt and Venous Thrombosis at Doses That Preserve Hemostasis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 933-933 ◽  
Author(s):  
Pancras C. Wong ◽  
Earl J. Crain ◽  
Donald J. Pinto ◽  
Carol A. Watson
Keyword(s):  
Venous Thrombosis ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Factor Xa ◽  
Arteriovenous Shunt ◽  
Thrombin Inhibitor ◽  
Phase Ii Trials ◽  
Prevention And Treatment ◽  
Fxa Inhibitor ◽  
Dose Dependent

Abstract Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor, which is currently in late stage clinical development for the prevention and treatment of thromboembolic diseases. The dose-dependent antithrombotic and antihemostatic profile of apixaban was determined in the rabbit models of arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT), and cuticle bleeding time (BT), and compared to those of the direct thrombin inhibitor lepirudin, the indirect FXa inhibitor fondaparinux and the oral anticoagulant warfarin. We induced the formation of thrombus in the AVST and VT models by placing threads in the extracorporeal shunt and vena cava, respectively, and bleeding by the incision of cuticles in anesthetized rabbits. In the AVST and VT prevention models, apixaban (0.03 to 3 mg/kg/h), lepirudin (0.006 to 0.75 mg/kg/h) and fondaparinux (0.01 to 1 mg/kg/h) were infused IV 30–60 min before the initiation of thrombosis. Warfarin (0.1 to 3 mg/kg/day) was administered orally for 4 days before the study. Control thrombus weight averaged 290±11 mg and 64±2 mg in AVST and VT, respectively, and control BT averaged 179±5 s (n=6 per group). Apixaban exhibited similar dose-related efficacy as lepirudin, fondaparinux, and warfarin in preventing AVST and VT. At doses that prevented 80 to 90% of thrombus formation in AVST and VT, apixaban, fondaparinux, lepirudin and warfarin increased BT by 20±2, 30±5, 500±10, 502±20%, respectively (n=6 per group). Doses for 50% reduction of control thrombus weight in AVST, VT were 0.27±0.03, 0.11±0.02 mg/kg/h IV for apixaban, 0.04±0.01, 0.05±0.01 mg/kg/h IV for lepirudin, 0.05±0.01, 0.05±0.005 mg/kg/h IV for fondaparinux and 0.53±0.04, 0.27±0.02 mg/kg PO for warfarin, respectively. To increase BT by 3-fold required higher doses of apixaban and fondaparinux (>3 mg/kg/h IV), lepirudin (0.24±0.05 mg/kg/h IV) and warfarin (0.70±0.07 mg/kg PO). In a VT treatment model, apixaban, lepirudin and fondaparinux, administered IV as a bolus injection supplemented with a continuous infusion after thrombus formation, were all able to arrest thrombus growth. However clot regression was only observed following administration of apixaban (0.6 mg/kg+0.87 mg/kg/h IV) where the preformed thrombus decreased from an initial weight of 38±2 mg (n=6) to 26±4 mg (n=6; P<0.05). In summary, apixaban and fondaparinux were effective in the prevention and treatment of experimental thrombosis at doses that preserve hemostasis in rabbits. Warfarin and lepirudin also prevented thrombus formation but with greater increases in BT. Furthermore, these standard anticoagulant agents have well-known limitations including narrow therapeutic index, frequent laboratory monitoring, or the requirement of parenteral administration. The favorable preclinical antithrombotic and antihemostatic profile of apixaban demonstrated here is consistent with clinical efficacy and safety results in recent Phase II trials, and indicates that direct inhibition of FXa with apixaban is a promising approach for the prevention and treatment of venous thromboembolism.

Dopaminergic modulation of respiratory motor output in peripherally chemodenervated goats

1998 ◽  
Vol 85 (3) ◽  
pp. 946-954 ◽  
Author(s):  
Ken D. O’Halloran ◽  
Patrick L. Janssen ◽  
Gerald E. Bisgard
Keyword(s):  
Carotid Body ◽  
Inhibitory Effect ◽  
Motor Output ◽  
High Dose ◽  
Inhibitory Effects ◽  
Before And After ◽  
Ventilatory Effect ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

We examined the ventilatory effects of exogenous dopamine (DA) and norepinephrine (NE) administration in chloralose-anesthetized, paralyzed, artificially ventilated adult goats before and after carotid body denervation (CBD). Intravenous (iv) DA bolus injections and slow iv infusions caused dose-dependent inhibition of phrenic nerve activity (PNA) in carotid body (CB)-intact animals during normoxia and hyperoxia but not during hypercapnia. NE administration in CB-intact goats caused dose-dependent inhibition of PNA of similar magnitude to DA trials. The DA D2-receptor agonists quinelorane and quinpirole inhibited PNA, whereas the DA D1-receptor agonist SKF-81297 had no effect. After CBD, the ventilatory depressant effects of DA persisted, but responses were significantly attenuated compared with CB-intact trials. CBD abolished the inhibitory effect of low-dose NE administration but did not alter ventilatory responses to high-dose NE injection. The peripheral DA D2-receptor antagonist domperidone substantially attenuated the inhibitory effects of DA bolus injections and infusions and reversed the inhibitory ventilatory effect of high-dose DA administration to excitation in some animals. The α-adrenoceptor antagonist phentolamine had no effect on DA-induced ventilatory depression. β-Adrenoceptor stimulation with isoproterenol produced similar hemodynamic effects to DA administration but had no effect on PNA. We conclude that DA and NE exert both CB-mediated and non-CB-mediated inhibitory effects on respiratory motor output in anesthetized goats. The ventilatory depressant effects that persist in peripherally chemodenervated animals are DA D2-receptor mediated, but their exact location remains speculative.

Differences between antigenic determinants of pig and cat zona pellucida proteins

Reproduction ◽  
2000 ◽  
pp. 15-23 ◽  
Author(s):  
K Jewgenow ◽  
M Rohleder ◽  
I Wegner
Keyword(s):  
In Vitro Fertilization ◽  
Zona Pellucida ◽  
Antigenic Determinants ◽  
Vitro Fertilization ◽  
Contraceptive Vaccine ◽  
Sperm Binding ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Despite many efforts, the control of reproduction in feral cat populations is still a problem in urban regions around the world. Immunocontraception is a promising approach; thus the present study examined the suitability of the widely used pig zona pellucida proteins (pZP) for contraception in feral domestic cats. Purified zona pellucida proteins obtained from pig and cat ovaries were used to produce highly specific antisera in rabbits. Antibodies against pZP raised in rabbits or lions were not effective inhibitors of either in vitro sperm binding (cat spermatozoa to cat oocytes) or in vitro fertilization in cats, whereas antibodies against feline zona pellucida proteins (fZP) raised in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology of ovaries confirmed these results, showing crossreactivity of anti-fZP sera to fZP and to a lesser extent to pZP, but no interaction of anti-pZP sera with fZP. It is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic determinants, making the use of pZP vaccine in cats questionable. A contraceptive vaccine based on feline zona pellucida determinants will be a better choice for the control of reproduction in feral cats if immunogenity can be achieved.

Antioxidant effects and in vitro cytotoxicity on human cancer cell lines of flavonoid-rich Flamboyant (Delonix regia (Bojer) Raf.) flower extract

2020 ◽  
Vol 21 ◽  
Author(s):  
Putthiporn Khongkaew ◽  
Phanphen Wattanaarsakit ◽  
Konstantinos I. Papadopoulos ◽  
Watcharaphong Chaemsawang
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Flower Extract ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Murine Leukemia Cell ◽  
Dose Dependent

Background: Cancer is a noncommunicable disease with increasing incidence and mortality rates both worldwide and in Thailand. Its apparent lack of effective treatments is posing challenging public health issues. Introduction: Encouraging research results indicating probable anti-cancer properties of the Delonix regia flower extract (DRE) have prompted us to evaluate the feasibility of developing a type of product for future cancer prevention or treatment. Methods and Results: In the present report, using High Performance Liquid Chromatography (HPLC), we demonstrate in the DRE, the presence of high concentrations of three identifiable flavonoids, namely rutin 4.15±0.30 % w/w, isoquercitrin 3.04±0.02 %w/w, and myricetin 2.61±0.01 % w/w respectively while the IC50 of DPPH and ABTS assay antioxidation activity was 66.88±6.30 µg/ml and 53.65±7.24 µg/ml respectively. Discussion: Our cancer cell line studies using the MTT assay demonstrated DREs potent and dose dependent inhibition of murine leukemia cell line (P-388: 35.28±4.07% of cell viability remaining), as well as of human breast adenocarcinoma (MCF-7), human cervical carcinoma (HeLa), human oral cavity carcinoma (KB), and human colon carcinoma (HT-29) cell lines in that order of magnitude. Conclusion: Three identifiable flavonoids (rutin, isoquercitrin and myricetin) with high antioxidation activity and potent and dose dependent inhibition of murine leukemia cell line and five other cancer cell lines were documented in the DRE. The extract’s lack of cytotoxicity in 3 normal cell lines is a rare advantage not usually seen in current antineoplastic agents. Yet another challenge of the DRE was its low dissolution rate and long-term storage stability, issues to be resolved before a future product can be formulated.

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

2020 ◽  
Vol 21 ◽  
Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Species ◽  
A549 Cells ◽  
Bactericidal Effect ◽  
Minimal Bactericidal Concentration ◽  
Viability Assay ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

scholarly journals In VitroActivities of Hexaazatrinaphthylenes against Leishmania spp.

2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Content Type ◽  
Inhibition Effect ◽  
Intracellular Amastigotes ◽  
Dependent Inhibition ◽  
Leishmania Spp ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Potential Use

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

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