scholarly journals Liposomes containing chelating agents. Cellular penetration and a possible mechanism of metal removal.

1975 ◽  
Vol 65 (1) ◽  
pp. 112-122 ◽  
Author(s):  
Y E Rahman ◽  
B J Wright
Keyword(s):  
Kupffer Cells ◽  
Chelating Agents ◽  
Metal Removal ◽  
Ethylenediaminetetraacetic Acid ◽  
Morphological Changes ◽  
Close Contact ◽  
Physiological Role ◽  
Cellular Membrane ◽  
Liposomal Membrane ◽  
Autophagic Vacuoles

Electron microscope studies were done on mouse liver, from 5 min to 8 wk after an intravenous injection of liposomes containing ethylenediaminetetraacetic acid (EDTA). Livers of mice receiving an injection of liposomes containing KCL instead of EDTA or an injection of a solution of EDTA were also examined. Liposomes were shown to be phagocytized by hepatocytes as well as by Kupffer cells within minutes after the injection. Initially, there was a close contact between the liposomal membrane and the cellular membrane, followed by an invagination of the latter and the formation of a distinct vesicle surrounding a single liposome or a cluster of several liposomes. No fusion between the liposomal membrane and the cell membrane was observed. Between 15 min and 6 h after liposome injection, the Kupffer cells were found to have an increased number of lysosomes and autophagic vacuoles. Within the latter, morphologically intact liposomes or remnants of liposomes could be seen. At 12 h after injection, a striking increase in macrophages was observed in the liver sinusoids of EDTA-liposome-injected mice, but not in those of KCl-liposome-injected mice. Within the macrophages, remnants of liposomes occasionally could be observed. However, the origin and the physiological role of these cells are unknown. In the hepatocytes, morphological changes were first observed 24 h after injection; there were large numbers of autophagic vacuoles, and some cells showed extensive areas of focal cytoplasmic degeneration. The morphology of the liver cells returned to normal about 7 days after injection. No morphological changes were observed in livers of mice receiving EDTA solution without liposomes. A possible mechanism by which the liposome-encapsulated chelating agents can successfully remove intracellular toxic metals is discussed. The use of liposomes as carriers seems to be a useful tool for intracellular delivery of chelating agents or drugs in general.

scholarly journals Upregulation of the Renin–Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Loris Zamai
Keyword(s):  
Chelating Agents ◽  
Ethylenediaminetetraacetic Acid ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Renin Angiotensin System ◽  
Experimental Models ◽  
Zinc Metalloprotease ◽  
Previous Hypothesis ◽  
Zinc Metalloproteases

The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to “clinical” manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.

Mobility of Chelated Radionuclides in Engineered Concrete Barriers

1992 ◽  
Vol 294 ◽  
Author(s):  
Craig A. Dicke ◽  
Robert W. Smith
Keyword(s):  
Citric Acid ◽  
Chelating Agents ◽  
Ethylenediaminetetraacetic Acid ◽  
Cobalt Complexes ◽  
Alkaline Ph ◽  
Pore Fluids ◽  
Concrete Barriers ◽  
Equilibrium Speciation ◽  
Low Level Radioactive Waste

ABSTRACTConcrete is a major component in many low-level radioactive waste (LLW) disposal facilities. The use of concrete is widespread because of its physical and structural properties and because it provides geochemical control on metal and radionuclide releases. Organic compounds are often disposed with radionuclides in LLW disposal facilities. Interactions between radionuclides and chelating agents must be evaluated to estimate mobility of radionuclides in concrete vaults. This paper quantifies the effects of two common organic components [citric acid and ethylenediaminetetraacetic acid (EDTA)] on radionuclide mobility in concrete barriers by using equilibrium geochemical calculations.Equilibrium speciation calculations indicate that some radionuclides are chelated in groundwater (pH 7) but are destabilized in the highly alkaline (pH 13) concrete pore fluids. Radionuclides complexed by EDTA and citrate are replaced by calcium in the concrete pore fluids. In addition, the citrate nuclide complex reacts to form uncomplexed citrate in concrete pore fluids. The chemical performance of concrete LLW disposal facilities should not be compromised by small amounts of chelating agents disposed with some radionuclides. However, EDTA may form significant nickel and cobalt complexes above the pH important in the long-term service life of concrete barriers.

scholarly journals An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure

2021 ◽  
Vol 22 (19) ◽  
pp. 10798
Author(s):  
Subramanian Boopathi ◽  
Adolfo B. Poma ◽  
Ramón Garduño-Juárez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Close Contact ◽  
Cellular Membrane ◽  
Therapeutic Strategies ◽  
Conformational Space ◽  
Disordered Proteins ◽  
Drug Candidate ◽  
Aβ Oligomers ◽  
Intrinsically Disorder

Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). Although experimental techniques rely on the measure of time- and space-average properties, they face severe difficulties in the investigation of Aβ peptide aggregation due to their intrinsically disorder character. Computer simulation is a tool that allows tracing the molecular motion of molecules; hence it complements Aβ experiments, as it allows to explore the binding mechanism between metal ions and Aβ oligomers close to the cellular membrane at the atomic resolution. In this context, integrated studies of experiments and computer simulations can assist in mapping the complete pathways of aggregation and toxicity of Aβ peptides. Aβ oligomers are disordered proteins, and due to a rapid exploration of their intrinsic conformational space in real-time, they are challenging therapeutic targets. Therefore, no good drug candidate could have been identified for clinical use. Our previous investigations identified two small molecules, M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine) and Gabapentin, capable of Aβ binding and inhibiting molecular aggregation, synaptotoxicity, intracellular calcium signaling, cellular toxicity and memory losses induced by Aβ. Thus, we recommend these molecules as novel candidates to assist anti-AD drug discovery in the near future. This review discusses the most recent research investigations about the Aβ dynamics in water, close contact with cell membranes, and several therapeutic strategies to remove plaque formation.

Recovery of Cu(II) by chemical reduction using sodium dithionite: effect of pH and ligands

2015 ◽  
Vol 72 (11) ◽  
pp. 2089-2094 ◽  
Author(s):  
Yi-Hsuan Chou ◽  
Jui-Hsuan Yu ◽  
Yang-Min Liang ◽  
Pin-Jan Wang ◽  
Chi-Wang Li ◽  
...  
Keyword(s):  
Metal Removal ◽  
Ethylenediaminetetraacetic Acid ◽  
Chemical Reduction ◽  
Metallic Copper ◽  
Sample Pretreatment ◽  
Copper Removal ◽  
Experimental Result ◽  
Molar Ratio ◽  
Metallic Nanoparticle ◽  
Industrial Sectors

Wastewaters containing Cu(II) and ligands are ubiquitous in various industrial sectors, and efficacy of copper removal processes, especially precipitation, is greatly compromised by ligands. Chemical reduction, being commonly employed for production of metal nanoparticles, is also effective for metal removal. Adjustment of pH and addition of ligands are important to control the particle size in metallic nanoparticle production. Exploiting the fact that ligands and metals coexist in many wastewaters, chemical reduction was employed to treat ligand-containing wastewater in this study. The experimental result shows that depending on pH, type of ligands, and copper:ligand molar ratio, copper could be removed by either the reduction or precipitation mechanism. Almost complete copper removal could be achieved by the reduction mechanism under optimal condition for solutions containing either EDTA (ethylenediaminetetraacetic acid) or citrate ligands. For solutions containing ammonia, depending on pH and Cu:ammonia molar ratio, copper was removed by both precipitation and reduction mechanisms. At pH of 9.0, formation of nano-sized particles, which readily pass through a 0.45 μm filter used for sample pretreatment before residual copper analysis, results in the lowest copper removal efficiency. Both cuprous oxide and metallic copper are identified in the solids produced, and the possible explanations are provided.

Gadolinium chloride, a Kupffer cell inhibitor, attenuates hepatic injury in a rat model of chronic cholestasis

2011 ◽  
Vol 30 (11) ◽  
pp. 1804-1810 ◽  
Author(s):  
Ali Zandieh ◽  
Seyedmehedi Payabvash ◽  
Parvin Pasalar ◽  
Afsaneh Morteza ◽  
Basira Zandieh ◽  
...  
Keyword(s):  
Kupffer Cell ◽  
Kupffer Cells ◽  
Enzyme Activities ◽  
Hepatic Injury ◽  
Morphological Changes ◽  
Gadolinium Chloride ◽  
Sham Operation ◽  
Chronic Cholestasis ◽  
Duct Ligation ◽  
Ductular Proliferation

The aim of the current study was to elucidate the effect of Kupffer cells inhibition on hepatic injury induced by chronic cholestasis. Sprague-Dawley rats underwent bile duct ligation (BDL) or sham operation and were treated with either saline solution or gadolinium chloride (GdCl3, a specific Kupffer cell inhibitor, 20 mg/kg i.p. daily). Serum and liver samples were collected after 28 days. Direct and total bilirubin concentrations and serum enzyme activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT) increased following BDL ( p < 0.01). On the contrary to bilirubin concentrations and AST activity, GdCl3 partially prevented the elevation in ALP, ALT and GGT enzyme activities ( p < 0.05). GdCl3 alleviated lipid peroxidation (reflected by malondialdehyde [MDA] concentration) and increased the activities of antioxidant enzymes (i.e. catalase and glutathione peroxidase) in liver samples after BDL ( p < 0.05). Fibrosis, ductular proliferation and portal inflammation were also scored in liver samples. Among morphological changes appeared following BDL (i.e. marked fibrosis, portal inflammation and ductular proliferation); only ductular proliferation was not alleviated by GdCl3. Therefore, Kupffer cells inhibition has beneficial effects against the development of hepatic injury induced by chronic cholestasis.

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