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La Medicina Del Lavoro 2006Antimony, which was already well known to the ancients, in the Middle Ages was known as Lupus metallorurn--the grey wolf--a key material in alchemists' attempts at...
Antimony, which was already well known to the ancients, in the Middle Ages was known as Lupus metallorurn--the grey wolf--a key material in alchemists' attempts at purifying gold. Over subsequent centuries antimony returned within the bounds of conventional scientific and experimental knowledge, but inspired numerous studies, works of literature and investigations in important fields of medicine. Antimony has always aroused more interest than one might expect from a simple metal. The fact that it has been used since ancient times in cosmetics and then in alchemy gave it both positive and negative connotations, reflecting its possible uses and the benefits for health but also the potential harm. For a certain period antimony was virtually the symbol for a range of uses in alchemy or empirical medicine, in the face of modern scientific knowledge, and aroused debate that went well beyond its actual physical and chemical properties. Bernardino Ramazzini's work in the 17th-18th centuries signalled the recognition that the use of antimony was linked to health risks. Today it is put to many uses in many fields of industry and medicine, so our interest in this metal is no longer exclusively a question of history, but is highly topical.
Topics: Antimony; Europe; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; History, Medieval
PubMed: 17009674
DOI: No ID Found -
Acta Tropica Jun 2022Clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of human leishmaniasis. Trypanothione metabolism,...
Clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of human leishmaniasis. Trypanothione metabolism, the main form of thiol, has shown to play a central role in antimony resistance of laboratory-generated resistant Leishmania spp. and field-isolated resistant L. donovani; but the mechanism of antimony resistance in the clinical isolates of L. tropica causing anthroponotic cutaneous leishmaniasis (ACL) is less studied. Patients were selected among confirmed positive ACL cases who referred to Pasteur Institute of Iran, Tehran, from endemic regions of north-east and south of Iran. L. tropica clinical isolates were collected from patients who were either treatment-responsive (MAS=S1 to S5) or unresponsive (MAR=R1 to R4) to Glucantime® (meglumine antimoniate=MA). Isolates were tested for sensitivity to trivalent antimony (SbIII) in promastigotes and to pentavalent antimony (SbV) in intracellular amastigotes stages. Intracellular thiol levels were assayed and trypanothione-dependent components, including trypanothione reductase (TR) and tryparedoxin peroxidase I (TryP) were analysed at protein level and enzymatic activity in isolates. The MAR isolates had an approximate two fold increase in the levels of intracellular thiols (P< 0.05) accompanied by an average 5-10 fold increase in in vitro resistance to antimony. TryP was amplified at the protein level in all MAR strains as compared to the MAS strains (range: 2.8-5.6 fold). All MAR isolates metabolized HO at higher rates than MAS isolates (8.55±0.75 nmol/min/mg vs. 3.14±0.36 nmol/min/mg) (P< 0.05). In addition, levels of TryR protein were also markedly elevated in 3 out of 4 MAR isolates (range: 2.2-4.1 fold). This was accompanied by overexpressed TryR activity (mean level of 46.83±2.43 for extracts of MAR vs. 20.98±3.02 for MAS strains) (P< 0.05). Elevated levels of TryP, active enzyme in peroxide detoxification, were observed in MAR parasites resulting in an increased metabolism of HO. TryR activity was overexpressed on average in extracts of MAR strains, but not in all isolates. Enhanced anti-oxidant defenses through thiol metabolism may play a significant role in clinical resistance of ACL patients to Glucantime.
Topics: Antimony; Antiprotozoal Agents; Drug Resistance; Humans; Hydrogen Peroxide; Iran; Leishmania tropica; Leishmaniasis, Cutaneous; Meglumine Antimoniate; NADH, NADPH Oxidoreductases; Peroxidases; Plant Extracts; Protozoan Proteins; Sulfhydryl Compounds
PubMed: 35276060
DOI: 10.1016/j.actatropica.2022.106392 -
Human & Experimental Toxicology Apr 19981. The aerobic filamentous fungus S. brevicaulis IMI 17297 methylated antimony from Sb2O3 substrate, with the formation of gaseous trimethylantimony (TMA). No evidence...
1. The aerobic filamentous fungus S. brevicaulis IMI 17297 methylated antimony from Sb2O3 substrate, with the formation of gaseous trimethylantimony (TMA). No evidence was found for the generation of other gaseous antimony compounds by this organism. 2. Biovolatilization of inorganic antimony was greatest during cultivation of the fungus on solid media at 25 degrees C, and occurred more readily from antimony (III) substrates than from antimony (V) substrates. 3. Under simulated cot environment conditions (CO2 enriched atmosphere, 33 degrees C) the fungus exhibited an altered morphology and a reduced capability to volatilize inorganic antimony from the pure compound. 4. No evidence of antimony biovolatilization from cot mattress PVC was found, unless antimony was released from PVC by heat treatment (at 80 or 100 degrees C). 5. These data suggest that normal cot environment conditions are non-optimal for volatilization of antimony by S. brevicaulis, and that Sb2O3 in cot mattress PVC is not bioavailable. 6. Cot mattress isolates of S. brevicaulis also volatilized antimony (not encapsulated by PVC), whereas those of other filamentous fungi (Penicillium spp., Aspergillus niger, Aspergillus fumigatus, Alternaria sp.) and of bacteria (Bacillus spp.) did not. 7. The oxidation products of TMA may be the true determinants of toxicity for biogenic antimony gases produced in an aerobic environment.
Topics: Antimony; Beds; Biodegradation, Environmental; Culture Media; Gas Chromatography-Mass Spectrometry; Humans; Infant Equipment; Infant, Newborn; Methylation; Mitosporic Fungi; Organometallic Compounds; Polyvinyl Chloride; Sudden Infant Death; Volatilization
PubMed: 9617636
DOI: 10.1177/096032719801700406 -
Archives of Dermatological Research Jan 2019Pentavalent antimonials remain the treatment of choice for all the clinical forms of leishmaniasis. The increasing rates of antimony resistance are becoming a serious...
Gene expression analysis of antimony resistance in Leishmania tropica using quantitative real-time PCR focused on genes involved in trypanothione metabolism and drug transport.
Pentavalent antimonials remain the treatment of choice for all the clinical forms of leishmaniasis. The increasing rates of antimony resistance are becoming a serious health problem in treatment of anthroponotic cutaneous leishmaniasis (ACL). Accordingly, unraveling molecular markers is crucial for improving medication strategies and monitoring of drug-resistant parasites. Different studies have suggested the importance of genes involved in trypanothione metabolism and drug transport. In this regard, present study was designed to investigate the RNA expression level of five genes including γ-GCS, ODC, TRYR (involved in trypanothione metabolism), AQP1 (acts in drug uptake) and MRPA (involved in sequestration of drug) in sensitive and resistant Leishmania tropica isolates. Seven antimony-resistant and seven antimony-sensitive L. tropica clinical isolates were collected from ACL patients. Drug sensitivity test was performed on the samples as well as reference strains; afterwards, gene expression analysis was performed on clinical isolates by quantitative real-time PCR. The results revealed that the average expression level of AQP1 gene was decreased (0.47-fold) in resistant isolates compared to sensitive ones whereas MRPA (2.45), γ-GCS (2.1) and TRYR (1.97) was upregulated in resistant isolates. The average expression of ODC (1.24-fold) gene was not different significantly between sensitive and resistant isolates. Our findings suggest that AQP1, MRPA, GSH1 and TRYR can be considered as potential molecular markers for screening of antimony resistance in some L. tropica clinical isolates.
Topics: Antimony; Antiprotozoal Agents; Biological Transport; Dose-Response Relationship, Drug; Drug Resistance; Glutathione; Leishmania tropica; Protozoan Proteins; Real-Time Polymerase Chain Reaction; Spermidine; Transcriptome
PubMed: 30390113
DOI: 10.1007/s00403-018-1872-2 -
Trends in Parasitology Apr 2011
Topics: Animals; Antimony; Antiprotozoal Agents; Drug Resistance; Humans; Leishmania; Leishmaniasis; Parasitic Sensitivity Tests
PubMed: 21216196
DOI: 10.1016/j.pt.2010.12.003 -
Journal of Environmental Monitoring :... Dec 2005Antimony is distributed in the environment in inorganic and organic species with different solubility and mobility characters. Here we investigate the transformation of...
Antimony is distributed in the environment in inorganic and organic species with different solubility and mobility characters. Here we investigate the transformation of antimony in view of biomethylation during sewage sludge fermentation as a case study for an anaerobic environment. Our approach was to identify if antimony methylation follows the Challenger pathway by using isotopically enriched antimonite (123Sb(v)). The antimony source was subjected to methylation in sewage sludge, an anaerobic dominant methanogenic Archaea community. The antimony species were determined in the gas phase using cryotrapping (CT)-GC-ICP-MS, and in the medium (sewage slude) by hydride generation (HG) prior CT-GC-ICP-MS. The determined 123/121Sb isotope ratios in the volatile trimethylstibine and non-volatile methylantimony species indicated that the methylation follows the proposed methylation pathway. With this approach we were able to quantify 123Sb incorporation into monomethyl-, dimethyl- and trimethylantimony, respectively. The incorporation decreased with further methylation from 91% to 82% and 73%. Volatilisation as trimethystibine was generally lower than 0.1%, however, up to 0.8% of added antimony was found methylated to methylantimony species and mainly accumulated in the cell. Moreover, antimony biomethylation was enhanced by stimulation of the anaerobic communities of methanogenic Archaea and sulfate reducing bacteria (SRB), with the methanogens showing a higher activity.
Topics: Antimony; Archaea; Fermentation; Isotopes; Methylation; Organometallic Compounds; Sewage; Sulfur-Reducing Bacteria
PubMed: 16307071
DOI: 10.1039/b509538g -
Molecules (Basel, Switzerland) Jun 2024Antimony (Sb) contamination poses significant environmental and health concerns due to its toxic nature and widespread presence, largely from anthropogenic activities....
Antimony (Sb) contamination poses significant environmental and health concerns due to its toxic nature and widespread presence, largely from anthropogenic activities. This study addresses the urgent need for an accurate speciation analysis of Sb, particularly in water sources, emphasizing its migration from polyethylene terephthalate (PET) plastic materials. Current methodologies primarily focus on total Sb content, leaving a critical knowledge gap for its speciation. Here, we present a novel analytical approach utilizing frontal chromatography coupled with inductively coupled plasma mass spectrometry (FC-ICP-MS) for the rapid speciation analysis of Sb(III) and Sb(V) in water. Systematic optimization of the FC-ICP-MS method was achieved through multivariate data analysis, resulting in a remarkably short analysis time of 150 s with a limit of detection below 1 ng kg. The optimized method was then applied to characterize PET leaching, revealing a marked effect of the plastic aging and manufacturing process not only on the total amount of Sb released but also on the nature of leached Sb species. This evidence demonstrates the effectiveness of the FC-ICP-MS approach in addressing such an environmental concern, benchmarking a new standard for Sb speciation analysis in consideration of its simplicity, cost effectiveness, greenness, and broad applicability in environmental and health monitoring.
Topics: Antimony; Polyethylene Terephthalates; Mass Spectrometry; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 38930935
DOI: 10.3390/molecules29122870 -
The Korean Journal of Parasitology Aug 2013The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran....
The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime®) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.
Topics: Amino Acid Transport Systems; Antimony; Antipruritics; Drug Resistance; Humans; Leishmania tropica; Leishmaniasis, Cutaneous; Protozoan Proteins; Ubiquitin
PubMed: 24039283
DOI: 10.3347/kjp.2013.51.4.413 -
Biological Trace Element Research Dec 2009The objective of the paper was to evaluate the influence of antimony (5+) on electrocardiographic changes in children with visceral leishmaniasis. The study was based on...
The objective of the paper was to evaluate the influence of antimony (5+) on electrocardiographic changes in children with visceral leishmaniasis. The study was based on weekly ECGs analysis of 87 children treated, from April 2001 to May 2006, with antimoniate N-methyl glucamine. Eligible subjects included children from 6 months to 12 years of age with weight of 6-34 kg. Forty-five children (52%) were males and forty-two (48%) were females. The cardiac response to antimony was significantly milder compared to the adult populations, so the usage of meglumine antimoniate is safer. Thus, during treatment sinus rhythm was maintained without ectopic beats. No changes were observed in the P wave and in PR interval. The QRS complex remained unaltered during the treatment, the amplitude being increased. The Sokolow's indexes exceeded normal values in one child on the first week and in eight children on the fourth. The prolongation of QTc occurred in ten patients. The T wave flattening was observed in seven children on the first week. In total, ECG abnormalities were detected in 34.4% of treatment courses, while in adults they were reported in 53.8%. Antimony therapy needs ECG monitoring of the cardiac function in order to prevent complications.
Topics: Antimony; Antiprotozoal Agents; Cardiovascular Abnormalities; Child; Child, Preschool; Electrocardiography; Female; Humans; Infant; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds
PubMed: 19424667
DOI: 10.1007/s12011-009-8387-9 -
Parasites & Vectors Aug 2021Leishmaniasis is a neglected tropical disease caused by several species of Leishmania. The resistance phenotype of these parasites depends on the characteristics of each... (Comparative Study)
Comparative Study
BACKGROUND
Leishmaniasis is a neglected tropical disease caused by several species of Leishmania. The resistance phenotype of these parasites depends on the characteristics of each species, which contributes to increased therapeutic failures. Understanding the mechanism used by the parasite to survive under treatment pressure in order to identify potential common and specific therapeutic targets is essential for the control of leishmaniasis. The aim of this study was to investigate the expression profiles and potential shared and specific resistance markers of the main Leishmania species of medical importance [subgenus L. (Leishmania): L. donovani, L. infantum and L. amazonensis; subgenus L. (Viannia): L. panamensis and L. braziliensis)] resistant and sensitive to trivalent stibogluconate (Sb).
METHODS
We conducted comparative analysis of the transcriptomic profiles (only coding sequences) of lines with experimentally induced resistance to Sb from biological replicates of five Leishmania species available in the databases of four articles based on ortholog attribution. Simultaneously, we carried out functional analysis of ontology and reconstruction of metabolic pathways of the resulting differentially expressed genes (DEGs).
RESULTS
Resistant lines for each species had differential responses in metabolic processes, compound binding, and membrane components concerning their sensitive counterpart. One hundred and thirty-nine metabolic pathways were found, with the three main pathways comprising cysteine and methionine metabolism, glycolysis, and the ribosome. Differentially expressed orthologous genes assigned to species-specific responses predominated, with 899 self-genes. No differentially expressed genes were found in common among the five species. Two common upregulated orthologous genes were found among four species (L. donovani, L. braziliensis, L. amazonensis, and L. panamensis) related to an RNA-binding protein and the NAD(P)H cytochrome-B5-oxidoreductase complex, associated with transcriptional control and de novo synthesis of linoleic acid, critical mechanisms in resistance to antimonials.
CONCLUSION
Herein, we identified potential species-specific genes related to resistance to Sb. Therefore, we suggest that future studies consider a treatment scheme that is species-specific. Despite the limitations of our study, this is the first approach toward unraveling the pan-genus genetic mechanisms of resistance in leishmaniasis.
Topics: Antimony; Antiprotozoal Agents; Drug Resistance; Leishmania; Metabolic Networks and Pathways; Protozoan Proteins; Transcriptome
PubMed: 34419127
DOI: 10.1186/s13071-021-04915-y