New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer DOI Open Access
George J. Kontoghiorghes

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13990 - 13990

Published: Nov. 13, 2022

There is new and increasing evidence from in vitro, vivo clinical studies implicating the pivotal role of iron associated metabolic pathways initiation, progression development cancer metastasis. New toxicity mechanisms pathways, as well genomic, transcription other factors, have been linked to many are related iron. Accordingly, a number targets for chelators identified characterized anticancer strategies, addition classical restriction of/reduction supply, inhibition transferrin delivery, ribonucleotide reductase DNA synthesis high antioxidant potential. The include removal excess iron-laden macrophages, which affects activity; modulation ferroptosis; ferritin control hyperferritinemia; hypoxia hypoxia-inducible factor (HIF); function molecular species such STEAP4 metalloreductase metastasis suppressor N-MYC downstream-regulated gene-1 (NDRG1); oxidative stress damage affecting mitochondrial function, etc. Many these new, but also previously known appear affect all stages cancer, drug resistance. Iron-chelating drugs especially deferiprone (L1), has shown recent fulfill multi-target above targets, proposed phase II trials patients. In contrast, lipophilic their complexes induction ferroptosis some refractory or recurring tumors resistance where effective treatments absent. need readdress therapy therapeutic strategies targeting multifactorial processes, including application multi-targeting involving iron-chelator complexes. protocols combinations with L1 chelating could increase activity, decrease metastasis, improve treatments, reduce overall survival

Language: Английский

Oxidative stress following spinal cord injury: From molecular mechanisms to therapeutic targets DOI

Mengsi Yu,

Zhiying Wang, Dongmin Wang

et al.

Journal of Neuroscience Research, Journal Year: 2023, Volume and Issue: 101(10), P. 1538 - 1554

Published: June 5, 2023

Abstract Spinal cord injury (SCI) is a medical condition that results from severe trauma to the central nervous system; it imposes great psychological and economic burdens on affected patients their families. The dynamic balance between reactive oxygen species (ROS) antioxidants essential for maintaining normal cellular physiological functions. As important intracellular signaling molecules, ROS regulate numerous activities, including vascular reactivity neuronal function. However, excessive can cause damage macromolecules, DNA, lipids, proteins; this eventually leads cell death. This review discusses mechanisms of oxidative stress in SCI describes some pathways after injury, with aim providing guidance development novel treatment strategies.

Language: Английский

Citations

36
Cyanidin-3-glucoside inhibits ferroptosis in renal tubular cells after ischemia/reperfusion injury via the AMPK pathway DOI Creative Commons
Yiwei Du, Xiao‐Kang Li, Tingting Wang

et al.

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: April 3, 2023

Abstract Background Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show C3G exerts nephroprotective against I/R-AKI related ferroptosis regulating AMPK pathway. Methods Hypoxia/reoxygenation (H/R)-induced HK-2 cells mice were treated or without inhibiting AMPK. The level intracellular free iron, expression ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) glutathione peroxidase (GPX4), levels markers 4-hydroxynonenal (4-HNE), reactive oxygen species (ROS) malondialdehyde (MDA) examined. Results We observed inhibitory effect in vitro vivo, was reversion excessive decrease 4-HNE, ROS, MDA ACSL4 expression, an increase GPX4 (GSH) levels. Notably, inhibition CC significantly abrogated models vivo vitro. Conclusion Our results provide new insight into activating

Language: Английский

Citations

27
Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications DOI Open Access
George J. Kontoghiorghes

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

Citations

27
Valorization of Fibrous Plant-Based Food Waste as Biosorbents for Remediation of Heavy Metals from Wastewater—A Review DOI Creative Commons
Ahasanul Karim, Zarifeh Raji, Antoine Karam

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(10), P. 4205 - 4205

Published: May 20, 2023

Mobilization of heavy metals in the environment has been a matter concern for several decades due to their toxicity humans, environments, and other living organisms. In recent years, use inexpensive abundantly available biosorbents generated from fibrous plant-based food-waste materials remove garnered considerable research attention. The aim this review is investigate applicability using food waste, which comprises different components such as pectin, hemicellulose, cellulose, lignin, wastewater. This contribution confirms that plant-fiber-based waste potential bind wastewater aqueous solutions. binding capacities these vary depending on source, chemical structure, type metal, modification technology applied, process conditions used improve functionalities. concludes with discussion arguments prospects, well future directions, support valorization an efficient promising strategy water purification.

Language: Английский

Citations

24
Rhodamine B- and coumarin-modified chitosan as fluorescent probe for detection of Fe3+ using quenching effect DOI

Seyyed-Mahdi Alavifar,

Marzieh Golshan,

Mahdi Hosseini

et al.

Cellulose, Journal Year: 2024, Volume and Issue: 31(5), P. 3015 - 3027

Published: March 1, 2024

Language: Английский

Citations

14
Unveiling the Chemistry of Citrus Peel: Insights into Nutraceutical Potential and Therapeutic Applications DOI Creative Commons
Hussan Munir, Sanabil Yaqoob, Kanza Aziz Awan

et al.

Foods, Journal Year: 2024, Volume and Issue: 13(11), P. 1681 - 1681

Published: May 27, 2024

The recent millennium has witnessed a notable shift in consumer focus towards natural products for addressing lifestyle-related disorders, driven by their safety and cost-effectiveness. Nutraceuticals functional foods play an imperative role meeting nutritional needs offering medicinal benefits. With increased scientific knowledge awareness, the significance of healthy lifestyle, including diet, reducing disease risk is widely acknowledged, facilitating access to diverse safer diet longevity. Plant-based rich phytochemicals are increasingly popular effectively utilized management. Agricultural waste from plant-based being recognized as valuable source nutraceuticals dietary interventions. Citrus peels, known flavonoids, emerging promising health-promoting ingredient. Globally, citrus production yields approximately 15 million tons by-products annually, highlighting substantial potential utilizing phyto-therapeutic nutraceutical applications. peels with concentrations ranging 2.5 5.5 g/100 g dry weight, depending on variety. most abundant flavonoids peel include hesperidin naringin, well essential oils monoterpenes like limonene. extracts exhibit high antioxidant capacity, DPPH radical scavenging activities 70 90%, comparable synthetic antioxidants BHA BHT. Additionally, present have been found properties, which can help reduce oxidative stress 30% cardiovascular 25%. Potent anti-inflammatory effects also demonstrated, inflammatory markers such IL-6 TNF-α up 40% cell culture studies. These findings highlight diet-based therapies.

Language: Английский

Citations

13
Tetracalcium phosphate/porous iron synergistically improved the mechanical, degradation and biological properties of polylactic acid scaffolds DOI

Wenhao Ding,

Meigui Chen,

Haocheng Du

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 271, P. 132530 - 132530

Published: May 21, 2024

Language: Английский

Citations

10
The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency DOI Open Access
George J. Kontoghiorghes

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

Citations

8
Multi-target-directed therapeutic strategies for Alzheimer’s disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition DOI Creative Commons

Jeasang Yoo,

Jimin Lee,

Byeongha Ahn

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review highlights the potential of multi-target-directed strategies that address amyloid-β aggregation, metal ion dyshomeostasis, and enzyme dysfunction, offering a comprehensive effective approach to treating Alzheimer's disease.

Language: Английский

Citations

1
Teucrium polium (L.): Phytochemical Screening and Biological Activities at Different Phenological Stages DOI Creative Commons
Majid Sharifi‐Rad, Paweł Pohl, Francesco Epifano

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(5), P. 1561 - 1561

Published: Feb. 25, 2022

The aim of the present study was to investigate changes in content phytochemical compounds and vitro antioxidant, antibacterial, anti-inflammatory activities Teucrium polium L. aerial parts root methanolic extracts at different phenological stages (vegetative, flowering, seeding). T. were analyzed using gas chromatography–mass spectrometry (GC-MS), their antioxidant properties tested with 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), ferrous ions (Fe2+), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. Forty-nine identified majority germacrene D, t-cadinol, β-pinene, carvacrol, bicyclogermacrene, α-pinene, limonene. results show that significantly differ between plant material used terms composition (total phenolic compounds, total flavonoids, alkaloids, saponin contents) bioactivities (antioxidant, anti-inflammatory) (p < 0.05). highest contents phenolics (72.4 ± 2.5 mg gallic equivalent (GAE)/g dry weight), flavonoids (36.2 3.1 quercetin (QE)/g alkaloids (105.7 2.8 atropine (AE)/g saponins (653 6.2 escin (EE)/g as well activities, measured for extract obtained flowering stage. minimum inhibitory concentration (MIC) values varied within 9.4–300 µg/mL, while bactericidal (MBC) 18.75–600 µg/mL. In addition, they more active on Gram-positive bacteria than Gram-negative bacteria. data this work confirm have significant biological activity hence can be pharmaceutical industry, clinical applications, medical research, cosmetic food industries.

Language: Английский

Citations

34