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1.
Proc Natl Acad Sci U S A ; 114(27): 6948-6953, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28634291

RESUMO

The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)]2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.


Assuntos
Ciclo Celular/efeitos dos fármacos , Complexos de Coordenação/toxicidade , Citotoxinas/toxicidade , Dano ao DNA , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , DNA/metabolismo , Ródio/toxicidade , Linhagem Celular Tumoral , Complexos de Coordenação/química , Citotoxinas/química , Humanos , Ródio/química
2.
Tumour Biol ; 36(5): 3325-36, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25528215

RESUMO

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.


Assuntos
Antineoplásicos/farmacologia , Compostos Férricos/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Ródio/farmacologia , Alanina Transaminase/sangue , Animais , Feminino , Compostos Férricos/toxicidade , Hepatócitos/patologia , Rim/fisiopatologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/mortalidade , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Ródio/toxicidade , Taxa de Sobrevida
3.
Neuro Endocrinol Lett ; 35 Suppl 2: 35-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25638364

RESUMO

OBJECTIVES: Road traffic pollutants and the residues of cytostatics that are widely used in anti-cancer therapy are a significant sources of platinum group elements (PGE; Pt, Pd and Rh) in environment. These metals can migrate into sewage and thus pollute surface waters. The purpose of our study was to evaluate the effect of PtCl4 on the antioxidant and enzymatic activity of duckweed (Lemna minor), a bioindicator of the aquatic environment. METHODS: The study was performed using a 7-day conventional test based on the OECD 221 (CSN EN ISO 20079)--Lemna sp. Growth Inhibition Test. We also conducted a microbiotest to analyse the effects of PtC4, PdCl2 and RhCl3 on the morphology and vegetative growth of colonies of this plant and compared their inhibitory effects during the microbiotest. RESULTS: We observed inhibition of colony growth and clear morphological changes. Antioxidant and enzymatic activities increased with platinum doses increased. The 168hEC50 of PtCl4 was 12.16 µM (95% confidence interval = 9.88-14.44) and the 168hEC50 of PdCl2 was 50.39 (95% confidence interval = 23.83-76.96). The greatest inhibition of growth by RhCl3 was observed at 25 µM. CONCLUSIONS: The obtained results suggest that L. minor phytotoxicity tests should be widely used in the biomonitoring.


Assuntos
Paládio/toxicidade , Plantas , Compostos de Platina/toxicidade , Ródio/toxicidade , Poluição Química da Água/efeitos adversos , Monitoramento Ambiental , Plantas/anatomia & histologia , Plantas/enzimologia , Plantas/metabolismo
4.
Neuro Endocrinol Lett ; 35 Suppl 2: 43-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25638365

RESUMO

OBJECTIVES: The platinum group elements (PGE) platinum (Pt), palladium (Pd), and rhodium (Rh) are used in automobile catalytic converters, from which they have been emitted into the environment to an increasing degree over the last 20 years. Despite the bioavailability of these metals to plants and animals, studies determining the effects of PGE on organisms are extremely rare. Enchytraeids are ecologically relevant soil organisms, due to their activity in decomposition and bioturbation in many soil types worldwide. DESIGN: The experiments were carried out as described in the OECD Guideline 220 [CSN EN ISO 16387--Soil quality--Effects of pollutants on Enchytraeidae (Enchytraeus sp.)--Determination of effects on reproduction]. The reproductive effects of platinum (PtCl4), palladium (PdCl2) and rhodium (RhCl3) were examined. The concentrations of PGE tested were as follows: 5, 10, 25, 50 and 100 µmol x L(-1) PdCl2; 50, 100, 150, 200 and 250 µmol x L-1 PtCl4/RhCl3. The EC50 (medium effective concentration) was determined after 28 days of exposure. The inhibition of the reproduction of PGE-exposed enchytraeids was compared against controls. RESULTS: Values of 28dEC50 of PtCl4, PdCl2 and RhCl3 amounted to 161.9 µmol x L(-1), 70.0 µmol x L(-1) and 246.6 µmol x L(-1), respectively. We can confirm that the relative order of toxicities is Pd (II) >Pt(IV) >>Rh(III). CONCLUSION: To the best of our knowledge, this is the first study to use Enchytraeus crypticus as an indicator species to assess the risk of soil contamination by platinum, palladium and rhodium. Results of this study contribute important data on the ecotoxicity of a rarely studied elements.


Assuntos
Oligoquetos/efeitos dos fármacos , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Poluentes do Solo/toxicidade , Solo , Animais , Monitoramento Ambiental
5.
Artigo em Inglês | MEDLINE | ID: mdl-24171412

RESUMO

Platinum group metals (PGMs), such as platinum (Pt), palladium (Pd), and rhodium (Rh), are of increasing concern due to rising anthropogenic input to aquatic systems. In this study, PGMs' effects on bioaccumulation and histopathological changes were investigated using Orconectes virilis, a native Hudson River crayfish, as a model. Organisms were exposed to varying concentrations of water-soluble PGM salts for 10 days. The following experimental treatments were established: 0.0, 1.0, 5.0, 10.0 ppm Pt(IV), 1.0 ppm Rh(III), 1.0 ppm Pd(II), and a PGM mix (1.0 ppm Pt(IV), Rh(III), Pd(II) each) dissolved in raw Hudson River water. Metal content in the tissue samples were analyzed by a Spectro Genesis ICP-OES. The relationship between Pt, Pd, and Rh concentrations in different treatments and observed behavioral changes during the experiment was analyzed through One-Way ANOVA Student-Newman-Keuls multiple comparison test (P ≤ 0.05). Paraffin sections, 6-µm-thick, were prepared in standard eosin-Y and hematoxylin-2 stain and examined for histological abnormalities within hepatopancreas, exoskeleton, brain, and ganglia tissue. Statistically significant differences in PGM bioaccumulation were observed in all organs, with highest concentrations found in the hepatopancreas, 81.68 mg g(-1) dw in 1.0 ppm Pd treatment, 20.03 mg g(-1) dw Rh in 1.0 ppm Rh treatment, and 81.58 mg g(-1) dw Pt in the 5.0 ppm Pt treatment. Pt bioaccumulation in the hepatopancreas and exoskeleton decreased at the highest Pt exposure treatment, suggesting severe structural damage to tissue. Hyper-segmentation of vacuoles and swelling of the vascular channels were observed in the hepatocyte structure of the hepatopancreas. Exoskeleton exhibited visible bands in the exocuticle indicating demineralization. Brain and ganglia demonstrated extensive vacuolization. Behavioral analysis showed an increase of maximum response intensity over the experimental period within each treatment. Bioaccumulation and cellular abnormalities observed in exposed aquatic organisms raise concern of PGM bio-magnification within the food chain and its effect on the environment and human health.


Assuntos
Astacoidea/efeitos dos fármacos , Platina/toxicidade , Animais , Astacoidea/metabolismo , Paládio/toxicidade , Ródio/toxicidade , Poluentes Químicos da Água/toxicidade
6.
Artigo em Inglês | MEDLINE | ID: mdl-24279618

RESUMO

Research was conducted to examine the hematological effects of heavy metals (platinum (Pt ((IV))), palladium (Pd ((II))), rhodium (Rh ((III))), antimony (Sb ((III)) and Sb ((V))), and silver nanoparticles (AgNPs)) on white blood cells in mammalian (rat) and avian (chick embryo) models. These metals are used in many everyday products and are accumulating in our environment. Six-week old Sprague-Dawley female rats were treated daily by gavage and six-day old, fertile, specific pathogen-free white leghorn strain chick embryos' eggs were injected on days 7 and 14 of incubation with 0.0, 1.0, 5.0 or 10.0 ppm concentrations of Pt ((IV)) and a platinum group metal (PGM) mix of Pt ((IV)), Pd ((II)) and Rh ((III)). Chick embryos were also tested with 1.0 or 5.0 ppm of antimony compounds (Sb ((III)) and Sb ((V))) and 0.0, 15.0, 30.0, 60.0, or 100.0 ppm of silver nanoparticles (AgNPs). After 8 weeks of treatment, blood was obtained from the rats by jugular cut down and from chick embryos on day 20 of incubation by heart puncture. Blood smears were made and stained and a differential white cell count was performed on each. Examination of the smears revealed unconventional dose responses, stimulation of the immune response, and decreases in leukocyte production with various metals and concentrations. Chick embryos responded differently than rats to Pt and the PGM mix; suggesting that species differences and/or stage of development are important components of response to heavy metals. Route of administration of the metals might also influence the response. All of the heavy metals tested affected the immune responses of the tested animals as demonstrated by changes in the types and numbers of leukocytes. Our findings warrant further research to determine the mechanism of these effects and to understand and prevent toxicological effects in humans and other living organisms.


Assuntos
Leucócitos/efeitos dos fármacos , Metais Pesados/toxicidade , Prata/toxicidade , Animais , Antimônio/toxicidade , Embrião de Galinha , Relação Dose-Resposta a Droga , Feminino , Contagem de Leucócitos , Leucócitos/imunologia , Linfa/efeitos dos fármacos , Linfa/imunologia , Metais Pesados/administração & dosagem , Nanopartículas/toxicidade , Paládio/toxicidade , Platina , Ratos , Ratos Sprague-Dawley , Ródio/toxicidade , Especificidade da Espécie
7.
Neuro Endocrinol Lett ; 34 Suppl 2: 5-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24362086

RESUMO

OBJECTIVES: Trace concentrations of the platinum group elements (PGE; Pt, Pd and Rh) are nowadays an irreplaceable part of environmental analysis and assessment. These rare elements are used as effective substances in automotive catalysts to reduce pollution by emissions originating from fuel combustion. Due to their harmful potential, it is necessary to monitor their content and behaviour in different samples. Effect assessment using ecotoxicological bioassays with organisms at different trophic levels can provide valuable pieces of information on the risk of chemical substances in the ecosystem. DESIGN: The experiments were carried out as described in the OECD Guideline 232 [CSN ISO 11267 - Soil quality - Inhibition of reproduction of Collembola (Folsomia candida) by soil pollutants]. The reproductive effects of palladium (PdCl2) and rhodium (RhCl3) were examined. Concentrations of PGE tested were as follows: 5, 10, 25, 50 and 100 µmol.L-1. The EC50 (medium effective concentration) was determined after 28 days of exposure. Inhibition of reproduction of PGE-exposed collembolans was compared against controls. RESULTS: Values of 28dEC50 of PdCl2 and RhCl3 amounted to 21.0 µmol.L-1 and 266.22 µmol.L-1, respectively. We can confirm that the relative order of toxicities is Pd (II) > Pt(IV) >> Rh(III). CONCLUSION: To the best of our knowledge, this is the first study to use Folsomia candida as an indicator species to assess the risk of soil contamination by palladium and rhodium. However, more toxicity data for various species are needed to evaluate the environmental risks of PGEs in soils.


Assuntos
Artrópodes/efeitos dos fármacos , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Poluentes do Solo/toxicidade , Solo/química , Animais , Artrópodes/fisiologia , Monitoramento Ambiental/métodos , Platina/análise , Reprodução/efeitos dos fármacos , Poluentes do Solo/análise
8.
Bull Environ Contam Toxicol ; 89(3): 686-92, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22885547

RESUMO

Quantitative changes in different cytokines were determined in serum of female Wistar rats exposed to Rhodium (III) chloride hydrate to evaluate its early effects on the immune system. Findings revealed an inhibitory effect of Rh salt since each cytokine, with the exceptions of IL-1α and IL-2 levels observed at the highest doses of exposure, was reduced compared to the controls and interestingly, the lowest doses induced the greatest inhibition. This generalized decrease of cytokine levels was not related to a specific cytokine pathway, and may suggest an anti-inflammatory role of Rh salt.


Assuntos
Ródio/toxicidade , Animais , Citocinas/metabolismo , Feminino , Ratos , Ratos Wistar , Testes de Toxicidade Subaguda
9.
ChemistryOpen ; 11(7): e202200019, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35212190

RESUMO

The cytotoxicities of seven dimeric metal species of the general formula [M(arene)Cl2 ]2 , commonly used as precursors for complex synthesis and deemed biologically inactive, are investigated in seven commonly employed human cancer cell lines. Four of these complexes featured a ruthenium(II) core, where p-cymene, toluene, benzene and indane were used as arenes. Furthermore, the osmium(II) p-cymene dimer, as well as the Cp* dimers of rhodium(III) and its heavier analogue iridium(III) were included in this work (Cp*=1,2,3,4,5-pentamethylcyclopentadienide). While the cytotoxic potencies of the ruthenium(II) and osmium(II) dimers are very low (or not even detectable at applicable concentrations), surprising activity, especially in cells from ovarian malignancies (with one or two-digit micromolar IC50 values), have been found for the rhodium(III) and iridium(III) representatives. This publication is aimed at all researchers using synthetic procedures based on functionalization of these dimeric starting materials to rationalize changes in biological properties, especially cytotoxicity in cancer cells.


Assuntos
Antineoplásicos , Neoplasias , Ródio , Rutênio , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Irídio , Osmio , Ródio/toxicidade
10.
Am J Ind Med ; 53(1): 42-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19953567

RESUMO

BACKGROUND: Whereas platinum salts are well known occupational allergens, rhodium salts have not been identified as inhalative sensitizing substances. METHODS: A 27-year-old atopic operator of an electroplating plant developed work-related shortness of breath and runny nose with sneezing after exposure to rhodium salts. Quantitative skin prick tests (SPT) and bronchial challenge tests with a dosimeter protocol were performed with quadrupling doses of the sodium chloride salts of rhodium (Na(3)RhCl(6)) and platinum (Na(2)PtCl(6)). RESULTS: The patient showed positive SPT reactions and positive bronchial immediate-type reactions with rhodium and platinum salts. Sensitivity to rhodium salt was much higher than to platinum salt; the molar concentrations differed by a factor of 256 in SPT and a factor of 16 in bronchial challenges. CONCLUSIONS: Rhodium salts should be considered as occupational immediate-type allergens.


Assuntos
Asma/induzido quimicamente , Galvanoplastia , Hipersensibilidade Imediata/diagnóstico , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Rinite Alérgica Perene/induzido quimicamente , Ródio/toxicidade , Adulto , Asma/diagnóstico , Testes de Provocação Brônquica , Relação Dose-Resposta a Droga , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Testes Intradérmicos , Masculino , Doenças Profissionais/diagnóstico , Platina/toxicidade , Rinite Alérgica Perene/diagnóstico
12.
Sci Total Environ ; 407(8): 2493-500, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19181366

RESUMO

Environmental concentrations of the platinum group elements (PGE) platinum (Pt), palladium (Pd) and rhodium (Rh) have been on the rise, due largely to the use of automobile catalytic converters which employ these metals as exhaust catalysts. It has generally been assumed that the health risks associated with environmental exposures to PGE are minimal. More recent studies on PGE toxicity, environmental bioavailability and concentrations in biologically relevant media indicate however that environmental exposures to these metals may indeed pose a health risk, especially at a chronic, subclinical level. The purpose of this paper is to review the most recent evidence and provide an up-to-date assessment of the risks related to environmental exposures of PGE, particularly in airborne particulate matter (PM). This review concludes that these metals may pose a greater health risk than once thought for several reasons. First, emitted PGE may be easily mobilised and solubilised by various compounds commonly present in the environment, thereby enhancing their bioavailability. Second, PGE may be transformed into more toxic species upon uptake by organisms. The presence of chloride in lung fluids, for instance, may lead to the formation of halogenated PGE complexes that have a greater potential to induce cellular damage. Third, a significant proportion of PGE found in airborne PM is present in the fine fraction that been found to be associated with increases in morbidity and mortality. PGE are also a concern to the extent that they contribute to the suite of metals found in fine PM suspected of eliciting a variety of health effects, especially in vulnerable populations. All these factors highlight the need to monitor environmental levels of PGE and continue research on their bioavailability, behaviour, speciation and associated toxicity to enable us to better assess their potential to elicit health effects in humans.


Assuntos
Poluentes Atmosféricos/toxicidade , Metais Pesados/toxicidade , Material Particulado/toxicidade , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/farmacocinética , Disponibilidade Biológica , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/farmacocinética , Paládio/análise , Paládio/farmacocinética , Paládio/toxicidade , Material Particulado/análise , Material Particulado/farmacocinética , Platina/análise , Platina/farmacocinética , Platina/toxicidade , Ródio/análise , Ródio/farmacocinética , Ródio/toxicidade , Medição de Risco
13.
Arh Hig Rada Toksikol ; 70(4): 224-231, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32623861

RESUMO

Measurable quantities of platinum, palladium, and rhodium, even in remote areas of the planet, evidence the global nature of pollution with these metals, mostly from catalytic converters of modern vehicles (other sources are jewellery production, chemical industry, and anticancer drugs). The amount of the platinum group metals (PGMs) emitted from automobile catalysts varies with the type, age, and condition of the engine and the catalyst, as well as the style of driving. Current literature suggests that the concentrations of these metals have increased considerably over the last twenty years, palladium concentrations in particular, as it has been proved more effective catalyst than platinum. However, whether and to what extent the emitted PGMs are toxic for people is still a controversy. The potential health risk from exposure to these elements is most likely for those living in urban environments with busy roads or along major highways. Because of the importance of PGMs and their trace levels in particulate matter, sensitive methods are required for reliable determination. This review discusses particular steps of analytical procedures for PGM quantification in airborne particulate matter and addresses the common preparation, detection, and determination methods.


Assuntos
Paládio/análise , Paládio/toxicidade , Material Particulado/análise , Platina/análise , Platina/toxicidade , Ródio/análise , Ródio/toxicidade , Automóveis , Indústria Química , Monitoramento Ambiental/métodos , Humanos
14.
Chemosphere ; 223: 738-747, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822635

RESUMO

Until recently, chemical derivatives of platinum group metals have not been in a systematic direct contact with living organisms. The situation has changed dramatically due to anthropogenic activity, which has led to significant redistribution of these metals in the biosphere. Millions of modern cars are equipped with automotive catalytic converters, which contain rhodium, palladium and platinum as active elements. Everyday usage of catalytic technologies promotes the propagation of catalyst components in the environment. Nevertheless, we still have not accumulated profound information on possible ecotoxic effects of these metal pollutants. In this study, we report a case of an extraordinarily rapid development of lethal toxicity of a rhodium (III) salt in the terrestrial plants Pisum sativum, Lupinus angustifolius and Cucumis sativus. The growth stage, at which the exposure occurred, had a crucial impact on the toxicity manifestation: at earlier stages, RhCl3 killed the plants within 24 h. In contrast, the salt was relatively low-toxic in human fibroblasts. We also address phytotoxicity of other common metal pollutants, such as palladium, iron, nickel and copper, together with their cytotoxicity. None of the tested compounds exhibited phytotoxic effects comparable with that of RhCl3. These results evidence the crucial deficiency in our knowledge on environmental dangers of newly widespread metal pollutants.


Assuntos
Poluentes Ambientais/análise , Plantas/efeitos dos fármacos , Ródio/toxicidade , Catálise , Humanos , Metais Pesados/efeitos adversos , Metais Pesados/análise , Emissões de Veículos/toxicidade
15.
Ecotoxicol Environ Saf ; 71(3): 722-30, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18206235

RESUMO

The risk associated with the inhalation of platinum group element (PGE) emissions from vehicle exhaust catalysts (VECs) has been investigated by extracting road dust and milled auto catalyst with simulated lung fluids. Gamble's solution (representative of the interstitial fluid of the deep lung) and artificial lysosomal fluid (ALF) (representative of the more acidic environment within the lung) were employed as extraction fluids. The highest PGE release was observed in ALF, implying that inhaled particles would have to be phagocytized before significant amounts of PGEs dissolve. The greatest percentage (up to 88%) of PGEs was released from road dust, possibly due to the presence of mobile PGE species formed in the roadside environment. Pt showed the highest absolute bioavailability, due to its greater concentration in the environmental samples. Pd and Rh had higher percentage of release, however, because of their more soluble nature. From the toxicological perspective, the results demonstrate potential health risks due to the likely formation of PGE-chloride complexes in the respiratory tract, such species having well-known toxic and allergenic effects on human beings and living organisms.


Assuntos
Poluentes Atmosféricos/toxicidade , Pulmão/efeitos dos fármacos , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Emissões de Veículos/toxicidade , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/metabolismo , Poeira/análise , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Humanos , Exposição por Inalação , Modelos Biológicos , Paládio/análise , Paládio/metabolismo , Platina/análise , Platina/metabolismo , Ródio/análise , Ródio/metabolismo , Medição de Risco , Emissões de Veículos/análise
16.
Sci Total Environ ; 615: 1396-1405, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29751444

RESUMO

The platinum group elements (PGE) platinum, palladium and rhodium gain increasing (eco-)toxicological interest due to their cumulative introduction into ecosystems. So far, most PGE exposure studies investigating biological availability, uptake and bioaccumulation of PGE as well as their effects on different toxicological endpoints were performed under non-standardized conditions which occasionally make an interpretation and comparison of the results difficult. Here we compare the results of different PGE exposure studies with zebra mussels (Dreissena polymorpha) showing influences due to the PGE source, the exposure medium, the exposure concentration and period as well as the test system. Problems associated to the performance and evaluation of these studies were identified and recommendations as well as needs for future studies are given. As nominal exposure concentrations often did not reflect real exposure conditions the reference for exposure concentration has to be chosen with caution, i.e. nominal versus quantified aqueous concentrations. The determination of bioaccumulation factors can be problematic when PGE concentrations in the exposure medium and in the test organism did not reach steady state even after several weeks of exposure. For future studies it would be advantageous to regularly correlating PGE bioaccumulation and biomarker responses to increase the knowledge on potential adverse effects of these metals, preferably using environmentally relevant PGE concentration scenarios. Many aspects discussed in the present study for zebra mussels and PGE can be transferred to other aquatic animals and other metals, respectively.


Assuntos
Dreissena/fisiologia , Monitoramento Ambiental , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Água Doce
17.
Int J Immunopathol Pharmacol ; 20(2 Suppl 2): 15-22, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17903351

RESUMO

Immunotoxicity of metal compounds is an issue of great importance due to the recent industrial application of metals with unknown toxicity on the immune system and the discovery of metal intermediary compounds not sufficiently studied yet. In this report we show results of our study on the immunotoxicity of the following metals: the Platinum group elements (Platinum, Palladium, Rhodium), Titanium and Arsenic. We applied functional and non functional assays and investigated both innate and adaptive immune systems, in particular, cell proliferation, cytokine production by PBMCs and O*2 production by neutrophils. We obtained the following results: only some Ti compounds (Titanocene, Ti ascorbate and Ti oxalate) show immunotoxicity. Trivalent As compounds (Sodium arsenite and tetraphenyl arsonium chloride) are more immunotoxic than the other investigated As compounds. Genotoxicity of Pt group compounds is in the following order: Pt > Rh > Pd. Immunotoxicity of Pt group compounds is in the following order: Pd > Pt > Rh. Lymphocytes and macrophages show a different reaction of neutrophils to metal toxicity. We can conclude that these studies show that metal immunotoxicity depends on speciation. In general speciation provides additional and often essential information in evaluating metal toxicity. However, there are many difficulties in applying speciation in investigating toxico-kinetic aspects to many metals, mainly due to the lack of information about the existence and significance of species and to the lack of analytical methods for measuring species in biological samples.


Assuntos
Sistema Imunitário/efeitos dos fármacos , Metais/toxicidade , Arsênio/toxicidade , Células Cultivadas , Citocinas/biossíntese , Humanos , Imunidade Inata/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Superóxidos/metabolismo , Titânio/toxicidade
18.
Anal Bioanal Chem ; 389(7-8): 2185-94, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17960368

RESUMO

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.


Assuntos
Técnicas Biossensoriais/métodos , Consumo de Oxigênio/fisiologia , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Consumo de Oxigênio/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo
19.
Environ Pollut ; 224: 368-376, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28222978

RESUMO

Mainly due to automobile traffic, but also due to other sources, the platinum group elements (PGE) platinum (Pt), palladium (Pd) and rhodium (Rh) are introduced into aquatic biotopes where they accumulate in sediments of lakes and rivers. However, the toxicity of these noble metals to aquatic organisms is not well understood and especially toxicity studies under standardized condition are lacking. Thus, the toxicity of Pt, Pd and Rh to Daphnia magna was tested in single metal exposure experiments according to OECD guideline 202. Immobility and lethality was recorded after 24 h and 48 h of exposure and EC50 and LC50, respectively, were determined. As the nominal exposure concentration of Pd differed significantly from the quantified concentration, the control of the real exposure concentration by chemical analysis is mandatory, especially for Pd. The toxicity decreased in the order Pd > Pt â‰« Rh with e.g. LC50(48 h) values of 14 µg/L for Pd, 157 µg/L for Pt and 56,800 µg/L for Rh. The exposure period had a clear effect on the toxicity of Pt, Pd and Rh. For Pt and Rh the endpoint immobility was more sensitive than the endpoint lethality whereas Pd toxicity was similar for both endpoints. The Hill slopes, which are a measure for the steepness of the concentration-response curves, showed no significant discrepancies between the different metals. The binary metal exposure to Pt and Pd revealed a more-than-additive, i.e. a synergistic toxicity using the toxic unit approach. The present study is a start to understand the toxicity of interacting PGE. The modes of action behind the synergistic effect are unclear.


Assuntos
Daphnia/efeitos dos fármacos , Platina/toxicidade , Ródio/toxicidade , Rios/química , Emissões de Veículos/análise , Poluentes Químicos da Água/análise , Animais , Monitoramento Ambiental , Paládio
20.
Environ Pollut ; 230: 31-39, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28644982

RESUMO

The aim of this study was to investigate chronic effects of the platinum-group elements (PGE) palladium (Pd), platinum (Pt) and rhodium (Rh) on the nematode Caenorhabditis elegans. Aquatic toxicity testing was carried out according to ISO 10872 by determining 96 h EC50 values for sublethal endpoints, including growth, fertility and reproduction. Single PGE standard solutions were used as metal source. Based on the EC50 values for Pt, reproduction (96 h EC50 = 497 µg/L) was the most sensitive endpoint followed by fertility (96 h EC50 = 726 µg/L) and growth (96 h EC50 = 808 µg/L). For Pd, no precise EC50 values could be calculated due to bell-shaped concentration response curves, but the 96 h EC50 for reproduction ranged between 10 and 100 µg/L. Pd and Pt had effects on all endpoints. With raising element concentrations reproduction was inhibited first. At a certain concentration, fertility was also affected, which in turn had an additional effect on reproduction. Growth inhibition can also lead to a loss of fertility if the worms do not reach an appropriate body size to become fertile. Rhodium showed no inhibition of any endpoint between concentrations of 100 to 10,000 µg Rh/L. The results of this study allow the following order of PGE with respect to decreasing toxicity to C. elegans: Pd > Pt ¼ Rh.


Assuntos
Substâncias Perigosas/toxicidade , Paládio/toxicidade , Platina/toxicidade , Ródio/toxicidade , Testes de Toxicidade Crônica , Animais , Caenorhabditis elegans/efeitos dos fármacos , Reprodução/efeitos dos fármacos
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