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Metallopharmaceuticals
Published in Varma H. Rambaran, Nalini K. Singh, Alternative Medicines for Diabetes Management, 2023
Varma H. Rambaran, Nalini K. Singh
In recent years, a number of studies have demonstrated the antidiabetic effects of oral tungstate (WO42–) (Figure 4.15) in diabetic animal models, and it has been touted as a more promising drug candidate than vanadium because of its relatively lower toxicity. Despite this slight edge over its competitor, the fear of the occurrence of cytotoxic events due to poor clearance is still a cause for concern (Domingo 2002).Structure of tungstate ion.
Separation Of The Bound And Unbound Forms Of The Radioactivity
Published in Erwin Regoeczi, Iodine-Labeled Plasma Proteins, 2019
By comparison to trichloroacetic acid, this is a rather complex reagent whereby a few introductory words about its chemistry seem in order. Characteristically, tungsten forms poly ions, which are either isopoly ions (containing W,O, and H), or heteropoly ions, i.e., those containing an additional element. The heteropoly tungstate ion forms when a tungstate solution is acidified in the presence of another oxo anion (in this case ). The acids of the heteropoly anions, such as phosphotungstic acid, are very soluble in water, alcohol or ether. On crystallization from H2O, phosphotungstic acid is obtained in a highly hydrated state. X-ray diffraction studies indicate that in the tungstate anion, W is placed in the center of an octahedron of six oxygen atoms. The structure of the heteropoly anion47-48 is more complex, consisting of four groups of octahedra. Thus, clearly, when phosphotungstate is used as a precipitant, the reagent forms large, “cage-like” structures around the points of interaction which co-sediment with the precipitated protein. Consequently, both the precipitable material and the precipitant are being depleted in the solution during the reaction. For a complete precipitation the reagent must therefore be in excess. According to Silverman and Glick,49 who studied the precipitation stoichiometry using 5% phosphotungstic acid at pH 2.0, the weight ratio of the protein to phosphotungstate in the precipitate formed with bovine albumin is 0.42, with bovine collagen 0.46, and rat skeletal muscle 0.44.
Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate
Published in Toxicology Mechanisms and Methods, 2021
Sherry Sachdeva, Wolfgang Maret
The 10-fold higher concentrations of tungstate in HEK293 cells in comparison to HepG2 cells (Figure 2) are in line with the published pharmacokinetic results of tungstate in rats. After administration of 10 mg/g tungstate to rats, 15-fold higher concentrations of tungstate in the kidneys (1.18 µg/g) were observed in comparison to the concentrations in the liver (0.08 µg/g) (Weber et al. 2008). Kidney cells seem to be adapted to this higher retention as they are much more resilient to the inhibitory effects of tungstate on energy metabolism (Figure 1). There is a specific transporter for uptake of molybdate. The human molybdate transporter (gene product of MFSD5, major facilitator superfamily domain-containing protein 5) is expressed ubiquitously in human cells (https://ebi10.uniprot.org/uniprot/Q6N075#expression). When expressed in Saccharomyces cerevisiae, a Km value of 550 nM for molybdate was determined (Tejada-Jiménez et al. 2011; Tejada-Jiménez and Schwarz 2014). Its transport properties for tungstate are unknown. Hence, it is not clear how and whether the human molybdate transporter discriminates between the two anions.
MiADMSA abrogates sodium tungstate-induced oxidative stress in rats
Published in Drug and Chemical Toxicology, 2022
Sherry Sachdeva, Ankita Sharma, S. J. S. Flora
Tungsten is a unique transition metal of group VI in the periodic table with an array of enviable attributes which include flexibility, great strength, good conductance, and a high melting point. These properties have led to an increase in the usage of tungsten commercially in a broad spectrum of industrial goods, ammunition, electronics, X-ray equipment, and implanted medical devices which has led to high levels of exposure to tungsten (Keith et al. 2007). However, there is a lacuna in the information regarding the potential human health risks of increased tungsten exposure which has led Environmental Protection Agency and the National Toxicology Program to identify tungsten as an emerging toxicant (Leffler and Kazantzis 2015, Bolt and Mann 2016, Steenstra et al. 2020). Sodium tungstate is the sodium salt of tungstic acid used as a source of tungsten for chemical synthesis. Sodium tungstate is a thermodynamically stable form showing chemical resistance in several oxidation states (0, +2, +3, +4, +5, and +6) (Bostick et al. 2018). Human exposure to tungsten can be either from natural sources or anthropogenic sources. The main source of occupational exposure of tungsten is via inhalation route which occurs during mining from its ore and also preparation of tungsten carbide products (Wasel and Freeman 2018). The oral route remains the primary route of exposure to tungsten, and soluble tungsten compounds. Pharmacokinetic studies have shown the rapid absorption of tungstate through the oral route, followed by metabolic reactions and rapid elimination via urine in both humans and laboratory animals (ATSDR 2005, Guandalini et al. 2011). Trace amounts of tungsten are also present in human serum and feces, with elimination approximately balancing intake of the metal (Leffler and Kazantzis 2015). Sodium tungstate, the oxidized naturally occurring water-soluble form released by weathering of rocks and soils, fertilizers, and sewage sludge escalates the risk of environmental tungstate exposure (Lemus and Venezia 2015, Liu et al. 2020). Sub-chronic exposure to sodium tungstate has been associated with renal dysfunction at the higher doses of 125 and 250 mg (McCain et al., 2007, 2008). Sodium tungstate exposure has also been found to induce mitochondrial dysfunction leading to the increased formation of ROS, TBARS generation, and loss of mitochondrial membrane potential (Witten et al. 2012, Cheraghi et al. 2019). In-vitro studies have also shown the cell cycle arrest and apoptosis-inducing properties of sodium tungstate in human peripheral blood lymphocytes (Osterburg et al. 2010).