Iron chelation therapy with deferiprone improves oxidative status and red blood cell quality and reduces redox-active iron in β-thalassemia/hemoglobin E patients

Morales, Noppawan Phumala; Rodrat, Supot; Piromkraipak, Pannaree; Yamanont, Paveena; Paiboonsukwong, Kittiphong; Fucharoen, Suthat

doi:10.1016/j.biopha.2021.112381

Cited by 13 publications

(10 citation statements)

References 39 publications

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“…In addition, we did not detect catalytic iron in the long-term treatment of deferiprone. 48 Our present data ( Figure 5c ) show that the molar ratio of deferiprone to iron was greater than 3 to 1 in almost all the data points. Therefore, we postulate that this form of iron does not contribute to increased oxidative stress.…”

Section: Discussionsupporting

confidence: 55%

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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Section: Discussionsupporting

confidence: 55%

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

Tran¹,

Sutcharitchan²,

Janprasit³

et al. 2022

DIC

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“…On the cellular level, the improved left-ventricular ejection function was suggested to be related to the iron chelation−antioxidant effects of L1 on endothelial cells [ 81 ]. Improvements in oxidative status and function including increases in glutathione levels were also observed in the red blood cells of iron loaded patients treated with L1 [ 82 ].…”

Section: Deferiprone Targeting Molecules and Metabolic Pathways Of Co...mentioning

confidence: 99%

“…The antioxidant potential of L1 has been previously established in many and different stages of oxidative stress toxicity using in vitro, in vivo and clinical models [ 57 , 58 , 68 , 69 , 74 , 81 , 82 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 ]. In this context, L1 is considered as one of the most potent antioxidant drugs in clinical use [ 58 ].…”

Section: Deferiprone Targeting Molecules and Metabolic Pathways Of Co...mentioning

confidence: 99%

Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology

Kontoghiorghes¹

2022

IJMS

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The need for preparing new strategies for the design of emergency drug therapies against COVID-19 and similar diseases in the future is rather urgent, considering the high rate of morbidity and especially mortality associated with COVID-19, which so far has exceeded 18 million lives. Such strategies could be conceived by targeting the causes and also the serious toxic side effects of the diseases, as well as associated biochemical and physiological pathways. Deferiprone (L1) is an EMA- and FDA-approved drug used worldwide for the treatment of iron overload and also other conditions where there are no effective treatments. The multi-potent effects and high safety record of L1 in iron loaded and non-iron loaded categories of patients suggests that L1 could be developed as a “magic bullet” drug against COVID-19 and diseases of similar symptomatology. The mode of action of L1 includes antiviral, antimicrobial, antioxidant, anti-hypoxic and anti-ferroptotic effects, iron buffering interactions with transferrin, iron mobilizing effects from ferritin, macrophages and other cells involved in the immune response and hyperinflammation, as well as many other therapeutic interventions. Similarly, several pharmacological and other characteristics of L1, including extensive tissue distribution and low cost of production, increase the prospect of worldwide availability, as well as many other therapeutic approach strategies involving drug combinations, adjuvant therapies and disease prevention.

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“…The iron-deferiprone bound is excreted from the body through the urine. Iron filtered by the glomerulus can be reabsorbed by the tubular system (Yatmark et al, 2016;Kontoghiorghes et al, 2020;Morales et al, 2022).…”

Section: Advances In Animal Andmentioning

confidence: 99%

“…Deferiprone is a bidentate oral chelator that forms an iron complex, which contains three molecules of deferiprone and one molecule of iron. Excretion of excess Fe bound by this compound is carried out by urine (Morales et al, 2022). Its small molecular shape has a neutral charge and hydrophilicity, which makes it easy to penetrate and mobilize excess iron from the tissues of all organs, including the heart and brain (Kontoghiorghes et al, 2020).…”

Section: Advances In Animal Andmentioning

confidence: 99%

Sappan Wood Ethanol Extract (Caesalpinia sappan L.) as Adjuvant and Substitute of Iron Chelator in Acute Iron Overload Rat Model

Pitaloka¹,

Alipin²,

Syamsunarno³

et al. 2022

AAVS

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I ron overload is a phenomenon caused by the accumulation of excess iron (Fe) in the body. Regular blood transfusion therapy in thalassemia patients can induce its accumulation (Mishra and Tiwari, 2013). Furthermore, the inability to produce hepcidin in hereditary hemochromatosis also causes this condition due to excess absorption (Kowdley et al., 2019). Iron can act as an electron carrier and catalyst for different processes, such as the Fenton reaction (Gattermann et al., 2021). The reaction often leads to the production of hydroxyl free radicals known as reactive oxygen species (ROS) that can induce oxidative stress and lipid peroxidation when their level exceeds that of antioxidants (Sousa et al., 2020). Iron overload in the body causes damage to body organs, such as the liver, heart, spleen, kidney, and brain (

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Iron chelation therapy with deferiprone improves oxidative status and red blood cell quality and reduces redox-active iron in β-thalassemia/hemoglobin E patients

Cited by 13 publications

References 39 publications

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

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

Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology

Sappan Wood Ethanol Extract (Caesalpinia sappan L.) as Adjuvant and Substitute of Iron Chelator in Acute Iron Overload Rat Model

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