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International Journal of Environmental... Dec 2010Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on... (Review)
Review
Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically.
Topics: Antimony; HIV Infections; Heart; Humans; Leishmaniasis; Occupational Exposure; Pancreatitis; Quality Control
PubMed: 21318007
DOI: 10.3390/ijerph7124267 -
International Journal of Environmental... Apr 2022Antimony has been known and used since ancient times, but its applications have increased significantly during the last two centuries. Aside from its few medical... (Review)
Review
Antimony has been known and used since ancient times, but its applications have increased significantly during the last two centuries. Aside from its few medical applications, it also has industrial applications, acting as a flame retardant and a catalyst. Geologically, native antimony is rare, and it is mostly found in sulfide ores. The main ore minerals of antimony are antimonite and jamesonite. The extensive mining and use of antimony have led to its introduction into the biosphere, where it can be hazardous, depending on its bioavailability and absorption. Detailed studies exist both from active and abandoned mining sites, and from urban settings, which document the environmental impact of antimony pollution and its impact on human physiology. Despite its evident and pronounced toxicity, it has also been used in some drugs, initially tartar emetics and subsequently antimonials. The latter are used to treat tropical diseases and their therapeutic potential for leishmaniasis means that they will not be soon phased out, despite the fact the antimonial resistance is beginning to be documented. The mechanisms by which antimony is introduced into human cells and subsequently excreted are still the subject of research; their elucidation will enable us to better understand antimony toxicity and, hopefully, to improve the nature and delivery method of antimonial drugs.
Topics: Antimony; Humans; Leishmaniasis; Minerals; Mining
PubMed: 35457536
DOI: 10.3390/ijerph19084669 -
Ecotoxicology and Environmental Safety Mar 2022Antimony (Sb) pollution has increased health risks to humans as a result of extensive application in diverse fields. Exposure to different levels of Sb and its compounds... (Review)
Review
Antimony (Sb) pollution has increased health risks to humans as a result of extensive application in diverse fields. Exposure to different levels of Sb and its compounds will directly or indirectly affect the normal function of the human body, whereas limited human health data and simulation studies delay the understanding of this element. In this review, we summarize current research on the effects of Sb on human health from different perspectives. First, the exposure pathways, concentration and excretion of Sb in humans are briefly introduced, and several studies have revealed that human exposure to high levels of Sb will cause higher concentrations in body tissues. Second, interactions between Sb and biomolecules or other nonbiomolecules affected biochemical processes such as gene expression and hormone secretion, which are vital for causing and understanding health effects and mechanisms. Finally, we discuss the different health effects of Sb at the biological level from small molecules to individual. In conclusion, exposure to high levels of Sb compounds will increase the risk of disease by affecting different cell signaling pathways. In addition, the appropriate form and dose of Sb contribute to inhibit the development of specific diseases. Key challenges and gaps in toxicity or benefit effects and mechanisms that still hinder risk assessment of human health are also identified in this review. Systematic studies on the relationships between the biochemical process of Sb and human health are needed.
Topics: Antimony; Environmental Pollution; Humans
PubMed: 35182796
DOI: 10.1016/j.ecoenv.2022.113317 -
Environmental Pollution (Barking, Essex... Apr 2017Elevated concentrations of antimony (Sb) in environmental, biological and geochemical systems originating from natural, geological and anthropogenic sources are of... (Review)
Review
Elevated concentrations of antimony (Sb) in environmental, biological and geochemical systems originating from natural, geological and anthropogenic sources are of particular global concern. This review presents a critical overview of natural geochemical processes which trigger the mobilization of Sb from its host mineral phases and related rocks to the surrounding environments. The primary source of Sb contamination in the environment is geogenic. The geochemical characteristics of Sb are determined by its oxidation states, speciation and redox transformation. Oxidative dissolution of sulfide minerals and aqueous dissolution are the most prevalent geochemical mechanisms for the release of Sb to the environment. Transformation of mobile forms of Sb is predominantly controlled by naturally occurring precipitation and adsorption processes. Oxyhydroxides of iron, manganese and aluminum minerals have been recognized as naturally occurring Sb sequestrating agents in the environment. Antimony is also immobilized in the natural environment via precipitation with alkali and heavy metals resulting extremely stable mineral phases, such as schafarzikite, tripuhyite and calcium antimonates. Many key aspects, including detection, quantification, and speciation of Sb in different environmental systems as well as its actual human exposure remain poorly understood. Identification of global distribution of most vulnerable Sb-contaminated regions/countries along with aquifer sediments is an urgent necessity for the installation of safe drinking water wells. Such approaches could provide the global population Sb-safe drinking and irrigation water and hinder the propagation of Sb in toxic levels through the food chain. Hence, raising awareness through the mobility, fate and transport of Sb as well as further transdisciplinary research on Sb from global scientific communities will be a crucial stage to establish a sustainable Sb mitigation on a global scale.
Topics: Adsorption; Animals; Antimony; Calcium Compounds; Environmental Exposure; Groundwater; Humans; Iron; Minerals; Oxidation-Reduction; Water Pollutants, Chemical
PubMed: 28190688
DOI: 10.1016/j.envpol.2017.01.057 -
Journal of Hazardous Materials May 2015The increasing interest in urban agriculture highlights the crucial question of crop quality. The main objectives for environmental sustainability are a decrease in... (Review)
Review
The increasing interest in urban agriculture highlights the crucial question of crop quality. The main objectives for environmental sustainability are a decrease in chemical inputs, a reduction in the level of pollutants, and an improvement in the soil's biological activity. Among inorganic pollutants emitted by vehicle traffic and some industrial processes in urban areas, antimony (Sb) is observed on a global scale. While this metalloid is known to be potentially toxic, it can transfer from the soil or the atmosphere to plants, and accumulate in their edible parts. Urban agriculture is developing worldwide, and could therefore increasingly expose populations to Sb. The objective of this review was in consequences to gather and interpret actual knowledge of Sb uptake and bioaccumulation by crops, to reveal investigative fields on which to focus. While there is still no legal maximal value for Sb in plants and soils, light has to be shed on its accumulation and the factors affecting it. A relative absence of data exists about the role of soil flora and fauna in the transfer, speciation and compartmentation of Sb in vegetables. Moreover, little information exists on Sb ecotoxicity for terrestrial ecosystems. A human risk assessment has finally been reviewed, with particular focus on Sb bioaccessibility.
Topics: Agriculture; Animals; Antimony; Biological Availability; Humans; Plants; Risk Assessment; Soil Pollutants
PubMed: 25726907
DOI: 10.1016/j.jhazmat.2015.02.011 -
Parasitology Research Nov 2011Leishmania is the causative agent of various forms of leishmaniasis, a significant cause of morbidity and mortality. The clinical manifestations of the disease range... (Review)
Review
Leishmania is the causative agent of various forms of leishmaniasis, a significant cause of morbidity and mortality. The clinical manifestations of the disease range from self-healing cutaneous and mucocutaneous skin ulcers to a fatal visceral form named visceral leishmaniasis or kala-azar. In the absence of any effective vaccine, the only means to treat and control leishmaniasis is affordable medication. The treatment choice is essentially directed by economic considerations; therefore, for a large majority of countries, chemotherapy relies only on the use of cheaper antimonial compounds. The emergence of antimonial therapy failure in India linked to proven parasite resistance has stressed questions about selective factors as well as transmission risk of drug resistance. Unfortunately, in most parts of the world, the frequency of parasite antimony resistance linked to treatment failure is unknown because of a lack of information on Leishmania antimony susceptibility. This information is crucial for addressing the risk of selection and transmission of drug-resistant parasites, particularly in areas where antimony is the only chemotherapeutic alternative. However, the poor knowledge about factors that favor selection of resistant parasites, the multiplicity of the agents that can play a role in the in vivo antileishmanial activity of antimony, and the lack of a standard protocol to diagnose and survey parasite resistance all contribute to insufficient monitoring of antimony resistance. In this review, we discuss on the factors potentially involved in the selection of antimony resistance in the field and discuss on the methods available for its diagnosis.
Topics: Antimony; Antiprotozoal Agents; Drug Resistance; Humans; India; Leishmania; Leishmaniasis; Treatment Failure
PubMed: 21800124
DOI: 10.1007/s00436-011-2555-5 -
Parasitology Jan 2024Leishmaniasis is a vector-borne parasitic disease caused by parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral... (Review)
Review
Leishmaniasis is a vector-borne parasitic disease caused by parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral complications. Treatment of this infection has been extremely challenging with the concurrent emergence of drug resistance. The differential gene expression and the discrepancies in protein functions contribute to the appearance of 2 distinct phenotypes: resistant and sensitive, but the current diagnostic tools fail to differentiate between them. The identification of gene expression patterns and molecular mechanisms coupled with antimony (Sb) resistance can be leveraged to prompt diagnosis and select the most effective treatment methods. The present study attempts to use comparative expression of Sb resistance-associated genes in resistant and sensitive , to disclose their relative abundance in clinical or selected isolates to gain an understanding of the molecular mechanisms of Sb response/resistance. Data suggest that the analysis of resistance gene expression would verify the Sb resistance or susceptibility only to a certain extent; however, none of the individual expression patterns of the studied genes was diagnostic as a biomarker of Sb response of . The findings highlighted will be useful in bridging the knowledge gap and discovering innovative diagnostic tools and novel therapeutic targets.
Topics: Leishmania; Antimony; Proteomics; Antiprotozoal Agents; Drug Resistance; Gene Expression
PubMed: 38012864
DOI: 10.1017/S0031182023001129 -
Acta Pharmacologica Sinica Aug 2008Antimony, a natural element that has been used as a drug for over more than 100 years, has remarkable therapeutic efficacy in patients with acute promyelocytic leukemia.... (Review)
Review
Antimony, a natural element that has been used as a drug for over more than 100 years, has remarkable therapeutic efficacy in patients with acute promyelocytic leukemia. This review focuses on recent advances in developing antimony anticancer agents with an emphasis on antimony coordination complexes, Sb (III) and Sb (V). These complexes, which include many organometallic complexes, may provide a broader spectrum of antitumoral activity. They were compared with classical platinum anticancer drugs. The review covers the literature data published up to 2007. A number of antimonials with different antitumoral activities are known and have diverse applications, even though little research has been done on their possibilities. It might be feasible to develop more specific and effective inhibitors for phosphatase-targeted, anticancer therapeutics through the screening of sodium stibogluconate (SSG) and potassium antimonyltartrate-related compounds, which are comprised of antimony conjugated to different organic moieties. For example, SSG appears to be a better inhibitor than suramin which is a compound known for its antineoplastic activity against several types of cancers.
Topics: Animals; Antimony; Antineoplastic Agents; Humans; Organometallic Compounds
PubMed: 18664320
DOI: 10.1111/j.1745-7254.2008.00818.x -
Cells Apr 2021parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. exhibits a high ability of developing drug resistance, and drug...
parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite's efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.
Topics: Antimony; Antiprotozoal Agents; Drug Resistance; Energy Metabolism; Leishmania tropica; Metabolome; Osmotic Pressure; Oxidative Stress
PubMed: 33946139
DOI: 10.3390/cells10051063 -
Cytokine Sep 2021The disease visceral leishmaniasis (VL) or kala azar is caused by the protozoan parasite, Leishmania donovani (LD). For many decades the pentavalent antimonial drugs... (Review)
Review
The disease visceral leishmaniasis (VL) or kala azar is caused by the protozoan parasite, Leishmania donovani (LD). For many decades the pentavalent antimonial drugs countered the successive epidemics of the disease in the Indian sub-continent and elsewhere. With time, antimony resistant LD (LD) developed and the drug in turn lost its efficacy. Infection of mammals with LD gives rise to aggressive infection as compared to its sensitive counterpart (LD) coupled with higher surge of IL-10 and TGF-β. The IL-10 causes upregulation of multidrug resistant protein-1 which causes efflux of antimonials from LD infected cells. This is believed to be a key mechanism of antimony resistance. MicroRNAs (miRNAs) are tiny post-transcriptional regulators of gene expression in mammalian cells and in macrophage play a pivotal role in controlling the expression of cytokines involved in infection process. Therefore, a change in miRNA profiles of macrophages infected with LD or LD could explain the differential cytokine response observed. Interestingly, the outcome of LD infection is also governed by the critical balance of pro- and anti-inflammatory cytokines which is inturn regulated by miRNA-Ago2 or miRNP complex and its antagonist RNA binding protein HuR. Here Ago2 plays the fulcrum whose phosphorylation and de-phosphorylation dictates the process; which in turn is controlled by PP2A and HuR. LD and LD upregulate PP2A and downregulate HuR at different magnitude leading to various levels of anti-inflammatory to proinflammatory cytokine production and resulting pathology in the host. While ectopic HuR expression alone is sufficient to clear LD infection, simultaneous upregulation of HuR and inhibition of PP2A is required to inhibit LD mediated infection. Therefore, tampering with miRNA pathway could be a new strategy to control infection caused by LD parasite.
Topics: Animals; Antimony; Argonaute Proteins; Drug Resistance; Gene Expression Regulation; Humans; Leishmania donovani; Leishmaniasis, Visceral; Protozoan Proteins
PubMed: 32861564
DOI: 10.1016/j.cyto.2020.155245