Antiplatelet activity of deferiprone through cyclooxygenase-1 inhibition

Tran, Ngan; Akkawat, Benjaporn; Morales, Noppawan Phumala; Rojnuckarin, Ponlapat; Luechapudiporn, Rataya

doi:10.1080/09537104.2019.1648782

Cited by 7 publications

(17 citation statements)

References 33 publications

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“…The platelet aggregation test was performed in accordance with [ 63 ], which was modified from the Born turbidimetric aggregometry method [ 45 ] using an aggregometer ALAT-2 laser aggregation analyzer (BIOLA, Moscow, Russia). PRP (300 µL) was set as 0% light transmission.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats

et al. 2021

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The inhibition of platelet aggregation, and the activity of oxidoreductases and microhemocirculation in a burn wound on the treatment of burns with wound dressings based on bacterial nanocellulose (BC)-zinc oxide nanoparticles (ZnO NPs)-betulin diphosphate (BDP) were studied. The control of the treatment by BC-ZnO NPs-BDP on burned rats by the noninvasive DLF method showed an increase in perfusion and the respiratory component in wavelet spectra, characterizing an improvement in oxygen saturation in the wound. The study on the volunteers’ blood found the inhibition of ADP-induced platelet aggregation by 30–90%. Disaggregation depends on the dose under the action of the ionized form of BDP and ZnO NPs-BDP in a phosphate buffer; it was reversible and had two waves. It was shown on rats that the specific activity of LDHreverse and LDHdirect (control-intact animals) on day 21 of treatment increased by 11–38% and 23%, respectively. The LDHreverse/LDHdirect ratio increased at BC-ZnO NPs-BDP treatment, which characterizes efficient NAD+ regeneration. AlDH activity increased significantly in the first 10 days by 70–170%, reflecting the effectiveness of the enzyme and NAD+ in utilizing toxic aldehydes at this stage of burn disease. The activities of GR and G6PDH using NADP(H) were increased with BC-ZnO NPs-BDP treatment.

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Section: Methodsmentioning

confidence: 99%

The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats

et al. 2021

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“…Platelet aggregation test was performed as our previous study [33], which was modified from the Born turbidimetric aggregometry method [34] using an aggregometer (Ag-gRAM™, Helena laboratories, Beaumont, TX, USA). PRP (200 µL) as 0% light transmission and PPP (250 µL) was set as 100% light transmission.…”

Section: Platelet Aggregation Measurementmentioning

confidence: 99%

“…The lower binding affinity represents a higher inhibitory action. The docking results were visualized and analyzed using Discovery Studio software [33].…”

Section: Molecular Docking Studymentioning

confidence: 99%

“…After that, ADP (4 µmol/L) was added to induce platelet aggregation and the reaction was terminated by 0.5% ice-cold ethanol. The samples were then vortexed, sonicated, and centrifuged to obtain the supernatant [33]. The cAMP ELISA kit (Cayman) was used to perform this assay and the experiments were carried out according to the manufacturer's instructions.…”

Section: Measurement Of Camp Levelsmentioning

confidence: 99%

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Inhibitory Mechanisms of Lusianthridin on Human Platelet Aggregation

Swe

Sritularak

Rojnuckarin

et al. 2021

IJMS

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Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC50 of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC50 value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.

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“…Moreover, an in silico study demonstrated that deferiprone was able to bind with the active site of COX1, suggesting that inhibition of COX1 may contribute to the antiplatelet activity of deferiprone. 13 …”

Section: Introductionmentioning

confidence: 99%

Deferiprone, an iron chelator, alleviates platelet hyperactivity in patients with β-thalassaemia/HbE

Tran¹,

Sutcharitchan²,

Janprasit³

et al. 2022

DIC

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Background Hyperfunctional platelets play important roles in thromboembolism in patients with β-thalassaemia/ haemoglobin E (β-thal/HbE). Our previous study revealed ex vivo inhibitory effects of deferiprone on normal platelets. Herein, we aimed to investigate the in vivo effects on platelets in patients with β-thal/HbE. Methods A prospective, self-controlled clinical study on 30 patients with β-thal/HbE who had received therapeutic deferiprone (20.8–94.5 mg/kg/day) was conducted. The study included a 4-week washout period followed by 4 and 12 weeks of deferiprone treatment. Platelet aggregation was performed by a turbidimetric method. Levels of deferiprone and soluble platelet (sP)-selectin in serum were measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kit, respectively. Results The washout period significantly enhanced platelet hyperactivity both in patients who had undergone splenectomy and in those who had not. At 2 hours following the administration of a single dose of deferiprone, platelet sensitivity to ADP and arachidonic acid was significantly reduced. The inhibitory effects of deferiprone were gradually increased over the period of 4 and 12 weeks. Deferiprone also depressed sP-selectin levels, but the effect was stable over longer follow-up periods. Correlation analysis demonstrated the relationship between serum levels of deferiprone, sP-selectin, and platelet activities induced by ADP and arachidonic acid. Conclusion We first demonstrated the in vivo antiplatelet effect and benefit of short-term treatment of deferiprone in patients with β-thal/HbE. The impact on thrombotic outcomes deserves further study.

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Antiplatelet activity of deferiprone through cyclooxygenase-1 inhibition

Cited by 7 publications

References 33 publications

The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats

The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats

Inhibitory Mechanisms of Lusianthridin on Human Platelet Aggregation

Deferiprone, an iron chelator, alleviates platelet hyperactivity in patients with β-thalassaemia/HbE

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