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Photomicrographs of control, arsenic-exposed and treated mice brain cortex, hematoxylin and eosin staining, ×40 magnification. (A) Control group showing various types of normal neurons and glial cells arranged in several layers; (B) bulk MiADMSA (50 mg/kg) group showing no degenerative changes; (C) void nanoparticles (50 mg/kg) group showing similar morphology as shown by control brain cortex (A); (D) nano-MiADMSA (50 mg/kg) group showing no degenerative changes; (E) arsenic-exposed group showing severe chromatolysis and pyknosis (arrows) of neurons, gliosis and edema in cortex compared to (E); (F) group treated with bulk MiADMSA after arsenic exposure showing reduced severity of necrotic and degenerative lesions in brain cortex; (G) group treated with void nanoparticles after arsenic exposure showing pyknosis of cortical neurons along with gliosis; and (H) group treated with nano-MiADMSA after arsenic exposure showing mild degenerative changes compared to (E).
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Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticl...
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... Histopathological examination Histopathological changes in the brain cor- tex following exposure to arsenic are shown in figure 4. The cortex region of the control mice brain showed normal neurons and glial cells arranged in several layers (figure 4a). ...
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... Histopathological examination Histopathological changes in the brain cor- tex following exposure to arsenic are shown in figure 4. The cortex region of the control mice brain showed normal neurons and glial cells arranged in several layers (figure 4a). Ani- mals with bulk MiADMSA (50 mg/kg), void nanoparticle (50 mg/kg) or nano-MiADMSA (50 mg/kg) exposure did not show any histo- pathological alteration compared to control brain cortex ( figure 4B-D). Mice with arsenic exposure showed shrunken pyknotic neurons along with central chromatolysis, edema and mild-to- moderate gliosis (figure 4e). ...
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... with arsenic exposure showed shrunken pyknotic neurons along with central chromatolysis, edema and mild-to- moderate gliosis (figure 4e). Histomorphologi- cal changes, namely chromatolysis, gliosis and edema, in animals exposed to arsenic followed by void nanoparticle treatment ( figure 4g) showed similarity in the severity of lesions as shown by the animals with arsenic alone. Animals with arsenic exposure treated with nano-MiADMSA (50 mg/kg) ( figure 4H) or bulk MiADMSA (50 mg/kg) (figure 4f) showed minimal degenerative changes as shown in taBle 4. The kidneys of con- trol mice showed normal architecture (figure 5a). ...
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... cal changes, namely chromatolysis, gliosis and edema, in animals exposed to arsenic followed by void nanoparticle treatment ( figure 4g) showed similarity in the severity of lesions as shown by the animals with arsenic alone. Animals with arsenic exposure treated with nano-MiADMSA (50 mg/kg) ( figure 4H) or bulk MiADMSA (50 mg/kg) (figure 4f) showed minimal degenerative changes as shown in taBle 4. The kidneys of con- trol mice showed normal architecture (figure 5a). They showed normal glomerulus, Bowman's Table 4. Histopathological grading of the liver, kidney and brain following arsenic exposure with and without treatment in mice (n = 6). ...
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Citations
... In the pharmaceutical industry, the implementation of biocatalysis is needed and this approach should continue being investigated to enrich drug development and enhance new pharmacological values [2]. This approach has also been integrated to support the biodegradation of complex materials or to target the selective biosynthesis of special compounds that can be used as educts in medical or dental applications [3,4]. The selection of microbial strains or biocatalysts is based on the protein sequences of the target enzymes. ...
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... Studies on the protective role of nanoparticles of chelating agents against arseniasis are also being undertaken in a few laboratories. Yadav et.al., [61] showed better efficacy of nano-MiADMSA (50nm) than bulk MiADMSA in reducing oxidative stress and efficient removal of arsenic from blood and tissues of sodium arsenite treated Swiss albino mice. Histopathological observations and urinary level of 8-OHdG also proved better therapeutic efficacy of nano-MiADMSA than bulk MiADMSA. ...
Clinical management of arsenic poisoning has been a major concern especially in countries like Bangladesh., India., Taiwan., Chile, Hungary and Argentina. In recent past, therapeutic efficacy of chelating agents, vitamins, nutrients, antioxidants and hormones has been investigated in many laboratories. Whereas, arsenic can be chelated by several agents viz: British Anti Lewisite (BAL), unithiol (DMPS), succimer (DMSA), monoisoamyl dimercaptosuccinic acid (MiADMSA), monocyclohexyl dimercaptosuccinic acid (MchDMSA), coadministration of quercetin and MiADMSA and taurine and MiADMSA have been found to reduce arsenic burdeon more effectively than their individual treatments. There are convincing reports that non-enzymatic antioxidants i.e. ascorbic acid, alpha tocopherol, B carotene, N-acetyl cysteine, alpha lipoic acid, curcumin, GSH and selenium offer protection against arseniasis by reducing oxidative stress. Melatonin, a product of pineal gland being a strong free radical scavenger possesses immense therapeutic importance against arseniasis. Thyroid hormones too influence arsenic toxicity. All these studies made in experimental animals have been briefly described in this review. However, cohorts made in human population are insignificant. Suitable clinical trials using these therapeutic agents individually or in combination may lead to the discovery of a “magic bullet” against arseniasis.
... Monoisoamyl DMSA (MiADMSA) is a hydrophobic chelator and has surfaced as a potential lead molecule for the management of arsenic toxicity. Several studies have been conducted to evaluate its potential against arsenic toxicity, and MiADMSA depicted therapeutic benefits in all of these studies [Patwa and Flora, 2020;Sathua et al., 2020;Panghal et al., 2020;Quamar et al., 2019;Yadav et al., 2014;Ram Kumar et al., 2013;Flora et al., 2012]. MiADMSA appears more efficacious in reducing brain arsenic load than DMSA [Walker et al., 2013]. ...
Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.
... This makes them interesting as highly versatile building blocks, e.g., for anti-cancer and anti-tumor agents [1,2], as plasticizers [3], or as educts for further chemicals [4] (Figure 1, lower range, and Table 1). There is an increasing demand for these monoesters as monomeric linkers or spacer groups, especially in medicinal chemistry and for dental applications [5,6]. Figure 1. ...
Monoethyl adipate (MEA) is a highly valuable monoester for activating resistance mechanisms and improving protective effects in pathogen-attacked plants. The cutinase ACut2 from the non-conventional yeast Blastobotrys (Arxula) raffinosifermentans (adeninivorans) was used for its synthesis by the desymmetrization of dicarboxylic acid diester diethyl adipate (DEA). Up to 78% MEA with 19% diacid adipic acid (AA) as by-product could be synthesized by the unpurified ACut2 culture supernatant from the B. raffinosifermentans overexpression strain. By adjusting pH and enzyme concentration, the selectivity of the free ACut2 culture supernatant was increased, yielding 95% MEA with 5% AA. Selectivity of the carrier immobilized ACut2 culture supernatant was also improved by pH adjustment during immobilization, as well as carrier enzyme loading, ultimately yielding 93% MEA with an even lower AA concentration of 3-4%. Thus, optimizations enabled the selective hydrolysis of DEA into MEA with only a minor AA impurity. In the up-scaling, a maximum of 98% chemical and 87.8% isolated MEA yield were obtained by the adsorbed enzyme preparation with a space time yield of 2.6 g L-1 h-1. The high monoester yields establish the ACut2-catalyzed biosynthesis as an alternative to existing methods.
... Its lipophilic nature allows penetration inside the cells. MchDMSA and MmDMSA can be taken up by mouth, and studies on animal models showed that combination therapy of both agents reduces cadmium and arsenic levels significantly (Flora et al. 2011;Yadav et al. 2014). ...
So long as the natural resources are available below the ground, mining operations will continue. However, mining is not an easy task and the challenges faced by miners are enormous. One of the major problems is effective forecasting and mitigating the disasters, either caused by natural or by manmade factors. The disasters in the mines include fire, explosion, inundation, electrocution, roof collapse, ground-caving. Compared to the open cast mines, the underground mines are more vulnerable to mining accidents. Every year hundreds of miners die due to various mining accidents including leakage of poisonous gases, explosion of combustible natural gases such as methane, or malfunctioning of mining equipment. Disaster management is a multi-disciplinary task in which, involvement of policy makers is important. Nevertheless, on-site mining operations need careful monitoring, proper ergonomic considerations in workplace design, and a quick medical response system. The important objective of mine management is to prepare all the stakeholders for the worst-case scenario. Accidents are inevitable; however, they can be minimized, the damage can be controlled, and injuries could be prevented. During emergencies, a quick response can be assured by periodically conducting mock drills, awareness seminars and training, and quick availability of medical aid. Moreover, proper communication of workers in the hazard-prone areas and self-rescue techniques for miners would be immensely helpful to ensure safe mining. The real-time location-based analysis, GIS mapping, dust monitoring, remote sensing advanced techniques have a significant advantage in the prevention of mining disasters. Certain guidelines have been prepared by the policy makers which are useful to minimize disaster. The research and development activities are being conducted to provide better technology-oriented instruments in mining for a smoother and safe mine environment with low-risk operations.KeywordsMiningDisasterControlPrevention strategiesGIS mappingRemote sensing
... Its lipophilic nature allows penetration inside the cells. MchDMSA and MmDMSA can be taken up by mouth, and studies on animal models showed that combination therapy of both agents reduces cadmium and arsenic levels significantly (Flora et al. 2011;Yadav et al. 2014). ...
Industrial coal combustion produces fine and ultrafine particulate matter that pollute ambient air which seem to play an important role in triggering biological processes and induced inflammation, immunological reactions and cellular damage. Sometimes ultrafine particulate matter gain access to the systemic circulation and travel to vital organs where they cause diseases in lungs, heart and brain. The huge volume of CFA is creating a variety of problems for environment and health. The CFA comprises trace amount of heavy metals, including arsenic (As), lead (Pb), nickel (Ni), cadmium (Cd), thallium (Th), vanadium (V), selenium, and mercury (Hg). It enters the human body directly through inhalation, and absorption via skin, or indirectly via ingestion of contaminated food and water. Some nonessential heavy metals and particulate matter individually, or in combination with other components, accelerate the generation of reactive oxygen species and induce oxidative stress that contributes to inflammation, DNA mutation, and lipid & protein damage. As and Pb are most dangerous heavy metals from CFA reported carcinogenicity and neurotoxicity in human beings. The effect of metal toxicity in exposed population can be studied by measuring the alteration of biochemical parameters, oxidative stress markers, inflammatory, and genotoxicity markers. Proper recycling and utilization of the CFA as the value-added products such as manufacturing of refractory bricks, as a pozzolan to produce hydraulic cement or hydraulic plaster, and complete or partial replacement for Portland cement in concrete production; or even as a land-fill material during building construction. CFA has been explored as an alternative source of various valuable elements such as Al, Si, Fe and Ti. It can also reduce disposal cost and reduce the degradation of environment. Strict rules and regulations regarding the storage and disposal of CFA should be implemented to check the deleterious effects of this toxic byproduct.KeywordsAlpha-quartzCoal fly ashHeavy metalsHuman HealthKaoliniteLung diseasesMulliteOrthoclase
... Its lipophilic nature allows penetration inside the cells. MchDMSA and MmDMSA can be taken up by mouth, and studies on animal models showed that combination therapy of both agents reduces cadmium and arsenic levels significantly (Flora et al. 2011;Yadav et al. 2014). ...
The present study was conducted in the proximity of Futala Lake, which is an urban hotspot for locals and tourists, within the municipal limits of Nagpur city in Central India. In order to access the hazard potential of the silica pebbles laden soil spread over the catchment area of the Futala lake, we conducted a study of soil profiles, particle size distribution analysis, granulometric analysis, XRD studies, and trace elements geochemistry. The soil profile consists of four distinct zones; top zone dominated by grass, humus, roots, soil attached to the root and silica pebbles; followed by zone consisting of silica pebbles embedded within the soil and next zone of fragments of bedrock basalt and the underlying zone of bed rock basalt showing spheroidal weathering. The modal analysis using image capture technique estimated the population of silica pebbles in small channel ways to be up to 10% of the entire area. Results of particle size distribution have indicated that the percentage of crystalline quartz are alarmingly high. The major portion occupied by soil ranges between 85 to 99% whereas the silica pebbles weigh between 0.3 to 8%. The soil fraction in an average contains ~24 sand, 33% silt and clay up to 42%, indicating clay loam based on soil texture triangle. Respirable dust typically consists of particles less than 5 µm (µm). During the present study, alarmingly high level of mineralized dust (<2 µm) in the range of 29 to 37 percent were recorded. The XRD study also suggests the presence of smectite, kaolinite and vermiculite along with quartz which makes the dust more hazardous. Such a high concentration of mineralized silica with additional deleterious constituents is highly undesirable and puts the large urban population at the risk of silicosis, chronic bronchitis, COPD and autoimmune diseases. This possibility of geogenic health hazard was not reported earlier, and seldom beyond the active silica mining sites. If true, there is a possible demon in our backyard, we never knew it exists.KeywordsSilica pebblesGeogenic health hazard
... The contents like proteins, polysaccharides, teichoic acids, and peptidoglycans are present in the cell walls of gram-positive bacteria (Passot et al., 2015). The bacterial wall contents contain negatively charged functional groups, which act as the primary sites of metal ion sorption on the bacterial surfaces (Mishra et al., 2013;Yadav et al., 2014). The phosphate and carboxyl groups present in peptidoglycans and teichoic acid contents of the bacterial cell surface are the potential metal ion binding sites (Kazy et al., 2009). ...
Lead (Pb) is a pestilent and relatively nonbiodegradable heavy metal, which causes severe health effects by inducing inflammation and oxidative stress in animal and human tissues. This is because of its significant tolerance and capability to bind Pb (430 mg/L) and thermodynamic fitness to sequester Pb in the Freundlich model (R ² = 0.98421) in vitro. Lactobacillus acidophilus KLDS1.1003 was selected for further in vivo study both in free and maize resistant starch (MRS)–based microencapsulated forms to assess its bioremediation aptitude against chronic Pb lethality using adult female BALB/c mice as a model animal. Orally administered free and microencapsulated KLDS 1.1003 provided significant protection by reducing Pb levels in the blood (127.92 ± 5.220 and 101.47 ± 4.142 µg/L), kidneys (19.86 ± 0.810 and 18.02 ± 0.735 µg/g), and liver (7.27 ± 0.296 and 6.42 ± 0.262 µg/g). MRS-microencapsulated KLDS 1.0344 improved the antioxidant index and inhibited changes in blood and serum enzyme concentrations and relieved the Pb-induced renal and hepatic pathological damages. SEM and EDS microscopy showed that the Pb covered the surfaces of cells and was chiefly bound due to the involvement of the carbon and oxygen elements. Similarly, FTIR showed that the amino, amide, phosphoryl, carboxyl, and hydroxyl functional groups of bacteria and MRS were mainly involved in Pb biosorption. Based on these findings, free and microencapsulated L. acidophilus KLDS 1.0344 could be considered a potential dietetic stratagem in alleviating chronic Pb toxicity.
... It is newer class of chelating agents originated from the monoester of DMSA designed to improve metal chelation in terms of efficacy and affinity for the HM ions in comparison with existing chelating agents available presently (Yadav et al. 2014). The main aim of developing this molecule is to enhance tissue uptake of chelating moieties. ...
... In general, Cu and Zn are top most essential metals which have a crucial role in enzyme activity, required for regular functioning for the human body. Co-administration of chelating agent with essential metal ions like Cu and Zn exhibits significant role in the depletion of toxic metals, concomitantly maintaining metal and cofactors balance required for normal body function (Flora et al. 2008;Flora 2009;Yadav et al. 2014). Various combination therapies have been tabulated in Table 2. ...
Toxicity due to heavy metals (HM), specifically mercury (Hg), arsenic (As), lead (Pb), and cadmium (Cd) remains a challenge to scientists till date. This review gives insights into natural antidotes for the management and prevention of HM toxicity. Various databases such as PubMed, Embase, and Science Direct were searched for available facts on natural antidotes and their commercial products against HM toxicity till date. Toxicity owing to such metals needs prevention rather than therapy. Natural antidotes, fruits and vegetables, rich in antioxidant are the answers to such toxicities. Synthetic chelators impart a major drawback of removing essential metals required for normal body function, along with the toxic one. Natural antioxidants are bestowed with scavenging and chelation properties and can be alternative for synthetic chelating agents. Natural compounds are abundantly available, economic, and have minimal side effects when compared with classical chelators. Prevention is better than cure and thus adding plentiful vegetables and fruits to our diet can combat HM toxicity-related illness.
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... Other than significant and notable progress with the development of MiADMSA as the future antidote for arsenic, there has been very little progress in finding a safe and effective treatment for arsenic toxicity that has been reported to date. In a few cases, nanoparticulated drug delivery has come forward in the treatment of arsenic intoxication cases [9][10][11]. Nanomaterials such as liposomes, polymeric micelles, and phospholipid complexes have emerged as few promising carriers' dues to its prolonged blood circulation times, better permeability in the cytosolic site, biodegradability, resistance to metabolic processes, and reduced toxicity. ...
Chelation therapy is considered as a safe and effective strategy to combat metal poisoning. Arsenic is known to cause neurological dysfunctions such as impaired memory, encephalopathy, and peripheral neuropathy as it easily crosses the blood-brain barrier. Oxidative stress is one of the mechanisms suggested for arsenic-induced neurotoxicity. We prepared Solid Lipid nanoparticles loaded with Monoisoamyl 2, 3-dimercaptosuccinic acid (Nano-MiADMSA), and compared their efficacy with bulk MiADMSA for treating arsenic-induced neurological and other biochemical effects. Solid lipid nanoparticles entrapping MiADMSA were synthesized and particle characterization was carried out by transmission electron microscopy (TEM) and dynamic light scattering (DLS). An in vivo study was planned to investigate the therapeutic efficacy of MiADMSA-encapsulated solid lipid nanoparticles (Nano-MiADMSA; 50 mg/kg orally for 5 days) and compared it with bulk MiADMSA against sodium meta-arsenite exposed rats (25 ppm in drinking water, for 12 weeks) in male rats. The results suggested the size of Nano-MiADMSA was between 100−120 nm ranges. We noted enhanced chelating properties of Nano-MiADMSA compared with bulk MiADMSA as evident by the reversal of oxidative stress variables like blood δ-aminolevulinic acid dehydratase (δ-ALAD), Reactive Oxygen Species (ROS), Catalase activity, Superoxide Dismutase (SOD), Thiobarbituric Acid Reactive Substances (TBARS), Reduced Glutathione (GSH) and Oxidized Glutathione (GSSG), Glutathione Peroxidase (GPx), Glutathione-S-transferase (GST) and efficient removal of arsenic from the blood and tissues. Recoveries in neurobehavioral parameters further confirmed nano-MiADMSA to be more effective than bulk MiADMSA. We conclude that treatment with Nano-MiADMSA is a better therapeutic strategy than bulk MiADMSA in reducing the effects of arsenic-induced oxidative stress and associated neurobehavioral changes.
