Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12928 - 12928

Published: Aug. 18, 2023

Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions patients, including those with overload other forms toxicity. Excess load an adverse prognostic factor diseases can cause serious organ damage fatalities following chronic red blood cell transfusions in patients many conditions, hemoglobinopathies, myelodyspasia, hematopoietic stem transplantation. Similar toxicity excess body but at a slower rate disease progression found idiopathic haemochromatosis patients. deposition different regions the brain suspected has been identified by MRI T2* similar methods neurodegenerative diseases, Alzheimer’s Parkinson’s disease. Based on its role as major biological catalyst free radical reactions Fenton reaction, also implicated associated pathology tissue damage. Furthermore, recent discovery ferroptosis, which death program based generation membrane lipid oxidation, sparked thousands investigations association cardiac, kidney, liver, cancer infections. The implications labile, non-protein bound form complexes dietary molecules such vitamin C drugs doxorubicin xenobiotic relation to carcinogenesis are discussed. In each case toxicity, mechanistic insights, diagnostic criteria, molecular interactions design new effective therapeutic interventions future targeted strategies. particular, this approach successful treatment most loading conditions especially transition thalassemia from fatal due protocols resulting complete elimination

Language: Английский

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The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4654 - 4654

Published: April 25, 2024

The supply and control of iron is essential for all cells vital many physiological processes. All functions activities are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin chelator–iron complexes haem play major roles metabolism human physiology. Similarly, the mainstay treatments most common diseases metabolism, namely deficiency anaemia overload, involve iron–chelator iron-chelating drugs deferiprone (L1), deferoxamine (DF) deferasirox. Endogenous citric acid glutathione exogenous ascorbic also important homeostasis. Recent advances treatment effective ferric tri-maltol complex (feraccru or accrufer) transfusional overload using L1 L1/DF combinations have decreased associated mortality morbidity improved quality life millions patients. Many other chelating ciclopirox, dexrazoxane EDTA used daily by patients diseases. their metabolites iron-chelation capacity hydroxyurea, tetracyclines, anthracyclines aspirin, well dietary molecules gallic acid, caffeic quercetin, ellagic maltol phytochelators, known to interact affect related Different interactions observed presence essential, xenobiotic, diagnostic theranostic metal ions competing iron. Clinical trials Parkinson’s, Alzheimer’s neurodegenerative diseases, HIV infections, cancer, diabetic nephropathy inflammation, highlight importance chelation therapy clinical conditions. proposed use modulating ferroptosis signifies a new era design therapeutic strategies introduction artificial intelligence guidance optimal outcomes personalised medicine expected increase further impact medicine, survival metabolic disorders

Language: Английский

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Tumor iron homeostasis and immune regulation

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(2), P. 145 - 156

Published: Jan. 11, 2024

Language: Английский

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NDRG1 alleviates Erastin-induced ferroptosis of hepatocellular carcinoma

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 21, 2025

NDRG1, a cell differentiation-associated factor, has recently emerged as regulator ferroptosis. Nevertheless, its role in modulating ferroptosis within hepatocellular carcinoma (HCC) remains uncharacterized. The differential expression of NDRG1 and prognostic value were analyzed HCC using data from TCGA GEO. Ferroptosis HepG2 Huh7 cells was assessed flow cytometry, transmission electron microscopy, propidium iodide staining following knockdown shRNA. RNA-seq performed to characterize the mRNA profiles cells, identifying differentially expressed mRNAs (DE-mRNAs) NDRG1-related hub genes. overexpressed multiple malignant tumors, including HCC, associated with significantly poor prognosis patients. A nomogram model integrating clinical parameters demonstrated robust accuracy. potentiated erastin-induced alterations Fe2+, total ROS, lipid markers (PTGS2, ACSL4, GPX4, SLC7A11, GSH, GSSG), while exacerbating mitochondrial ultrastructural damage cells. Erastin induction elicited 1,056 DE-mRNAs, subsequent revealed 1,323 DE-mRNAs These are mainly involved metastasis, immunity, growth, ferroptosis, AMPK, MAPK, PI3K/AKT pathways. Moreover, potentially interacted HSPA8, CDH1, ALDOC, ANGPTL4, ANKRD37, CA9, ERBB3, FOS. qRT-PCR confirmed their changes consistent RNA-seq. exhibits strong predictive for accelerates tumor progression by suppressing

Language: Английский

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Deferiprone and Iron–Maltol: Forty Years since Their Discovery and Insights into Their Drug Design, Development, Clinical Use and Future Prospects

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4970 - 4970

Published: March 4, 2023

The historical insights and background of the discovery, development clinical use deferiprone (L1) maltol–iron complex, which were discovered over 40 years ago, highlight difficulties, complexities efforts in general orphan drug programs originating from academic centers. Deferiprone is widely used for removal excess iron treatment overload diseases, but also many other diseases associated with toxicity, as well modulation metabolism pathways. complex a recently approved increasing intake deficiency anemia, condition affecting one-third to one-quarter world’s population. Detailed into different aspects L1 are revealed, including theoretical concepts invention; discovery; new chemical synthesis; vitro, vivo screening; toxicology; pharmacology; optimization dose protocols. prospects application these two drugs discussed under light competing commercial centers regulatory authorities. underlying scientific strategies, limitations present global scene pharmaceuticals, highlighted, an emphasis on priorities emergency medicine development, roles community, pharmaceutical companies patient organizations.

Language: Английский

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Macromolecules incorporating transition metals in the treatment and detection of cancer and infectious diseases: Progress over the last decade

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 510, P. 215732 - 215732

Published: March 28, 2024

Language: Английский

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The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(7), P. 1016 - 1016

Published: July 18, 2023

The iron chelating orphan drug deferiprone (L1), discovered over 40 years ago, has been used daily by patients across the world at high doses (75–100 mg/kg) for more than 30 with no serious toxicity. level of safety and simple, inexpensive synthesis are some many unique properties L1, which played a major role in contribution transition thalassaemia from fatal to chronic disease. Other valuable clinical L1 relation pharmacology metabolism include: oral effectiveness, improved compliance compared prototype therapy subcutaneous deferoxamine; highly effective removal all iron-loaded organs, particularly heart, is target organ toxicity cause mortality thalassaemic patients; an ability achieve negative balance, completely remove excess iron, maintain normal stores rapid absorption stomach clearance body, allowing greater frequency repeated administration overall increased efficacy excretion, dependent on dose also concentration achieved site action; its cross blood–brain barrier treat malignant, neurological, microbial diseases affecting brain. Some differential pharmacological activity among generally shown absorption, distribution, metabolism, elimination, (ADMET) drug. Unique exhibited comparison other drugs include specific protein interactions antioxidant effects, such as transferrin lactoferrin; inhibition copper catalytic production free radicals, ferroptosis, cuproptosis; iron-containing proteins associated different pathological conditions. have attracted interest investigators repurposing use conditions, including cancer, neurodegenerative renal radical pathology, metal intoxication Fe, Cu, Al, Zn, Ga, In, U, Pu, diseases. Similarly, increase prospects wider optimizing therapeutic efforts fields medicine, synergies drugs.

Language: Английский

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Solution chemistry and anti-proliferative activity against glioblastoma cells of a vanadium(V) complex with two bioactive ligands

Frontiers in Chemical Biology, Journal Year: 2024, Volume and Issue: 3

Published: July 5, 2024

Introduction: Glioblastoma is a brain cancer difficult to treat but recently mixed-ligand vanadium(V) Schiff base/catecholato complexes have exhibited high in vitro anti-proliferative activity. Hence, we explored the activity of [V V OL 1 L 2 ], which contains two iron chelating ligands, 2-hydroxy-1-naphthylaldehyde iso -nicotinoyhydrazone (L H ) and clioquinol H). This complex was previously reported be very effective against Trypanosoma cruzi , causative agent Chagas disease. These studies possibility that compound with efficacy also has human glioblastoma cells. Since ] poorly soluble water ligand dissociated from upon addition an aqueous environment, understanding speciation important interpret its biological Methods: Stability cell media were followed by UV/Vis spectroscopy determine relevance T98G cells, measured absence presence Fe(III). Results Discussion: The current work demonstrated vanadium coordination had (T98G) line. enhanced effects cells could due either hydrolysis release toxic clioquinol, or rapid uptake lipophilic prior hydrolysis. showed at least part potent toxicity stemmed bioactive complex, depended on whether Fe(III) present. (O) H)] most remained intact and, hence, active. Thus, future development should focus one-ligand making any more soluble, stable solution, designed rapidly taken up diseased

Language: Английский

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Heavy Metal Contamination: Sources, Health Impacts, and Sustainable Mitigation Strategies with Insights from Nigerian Case Studies

F1000Research, Journal Year: 2025, Volume and Issue: 14, P. 134 - 134

Published: Jan. 27, 2025

Heavy metal contamination has gradually become a very much important significant global issue due to its continual existence in the environment and bioaccumulation ecosystems, posing deleterious risks human health. This review aims investigate sources, pathways, toxicological impacts of heavy metals such as cadmium, lead, mercury, arsenic, elucidating their health consequences plausible mitigation strategies. Furthermore, explores dual origins contamination; natural geological processes anthropogenic activities industrial emissions, mining, agricultural practices. These sip into soil, water, food chains, leading bioaccumulation, bio-magnification causing risks, including cardiovascular diseases, neurological disorders, reproductive toxicity. Additionally, addition indigenous case studies from Nigeria, lead poisoning Zamfara State Great Kwa River Cross Rivers underscores disproportionate impact pollution developing nations. reveal socio-economic environmental dimensions issue, providing contextual understanding region-specific vulnerabilities outcomes. To address these problems, evaluates already existing strategies, chelation therapy phytoremediation, while proposing sustainable, cost-effective solutions for reducing exposure mitigating impacts. It emphasizes importance integrative approaches involving policy, community engagement, technological innovations fight effectively. In conclusion, this seminar contributes toxicity, giving showcasing insights sources implications contamination. By integrating theoretical perspectives with practical solutions, provides robust framework informing policy makers advancing sustainable management practices.

Language: Английский

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Heavy Metal Contamination: Sources, Health Impacts, and Sustainable Mitigation Strategies with Insights from Nigerian Case Studies

F1000Research, Journal Year: 2025, Volume and Issue: 14, P. 134 - 134

Published: Feb. 18, 2025

Heavy metal contamination has gradually become a very much important significant global issue due to its continual existence in the environment and bioaccumulation ecosystems, posing deleterious risks human health. This review aims investigate sources, pathways, toxicological impacts of heavy metals such as cadmium, lead, mercury, arsenic, elucidating their health consequences plausible mitigation strategies. Furthermore, explores dual origins contamination; natural geological processes anthropogenic activities industrial emissions, mining, agricultural practices. These sip into soil, water, food chains, leading bioaccumulation, bio-magnification causing risks, including cardiovascular diseases, neurological disorders, reproductive toxicity. Additionally, addition indigenous case studies from Nigeria, lead poisoning Zamfara State Great Kwa River Cross Rivers underscores disproportionate impact pollution developing nations. reveal socio-economic environmental dimensions issue, providing contextual understanding region-specific vulnerabilities outcomes. To address these problems, evaluates already existing strategies, chelation therapy phytoremediation, while proposing sustainable, cost-effective solutions for reducing exposure mitigating impacts. It emphasizes importance integrative approaches involving policy, community engagement, technological innovations fight effectively. In conclusion, this seminar contributes toxicity, giving showcasing insights sources implications contamination. By integrating theoretical perspectives with practical solutions, provides robust framework informing policy makers advancing sustainable management practices.

Language: Английский

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