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1.
PLoS One ; 13(12): e0209413, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30586399

RESUMEN

In 2017, the International Agency for Research on Cancer classified welding fumes as "carcinogenic to humans" (Group 1). Both mild steel (MS) welding, where fumes lack carcinogenic chromium and nickel, and stainless steel (SS) increase lung cancer risk in welders; therefore, further research to better understand the toxicity of the individual metals is needed. The objectives were to (1) compare the pulmonary toxicity of chromium (as Cr(III) oxide [Cr2O3] and Cr (VI) calcium chromate [CaCrO4]), nickel [II] oxide (NiO), iron [III] oxide (Fe2O3), and gas metal arc welding-SS (GMAW-SS) fume; and (2) determine if these metal oxides can promote lung tumors. Lung tumor susceptible A/J mice (male, 4-5 weeks old) were exposed by oropharyngeal aspiration to vehicle, GMAW-SS fume (1.7 mg), or a low or high dose of surrogate metal oxides based on the respective weight percent of each metal in the fume: Cr2O3 + CaCrO4 (366 + 5 µg and 731 + 11 µg), NiO (141 and 281 µg), or Fe2O3 (1 and 2 mg). Bronchoalveolar lavage, histopathology, and lung/liver qPCR were done at 1, 7, 28, and 84 days post-aspiration. In a two-stage lung carcinogenesis model, mice were initiated with 3-methylcholanthrene (10 µg/g; intraperitoneal; 1x) or corn oil then exposed to metal oxides or vehicle (1 x/week for 5 weeks) by oropharyngeal aspiration. Lung tumors were counted at 30 weeks post-initiation. Results indicate the inflammatory potential of the metal oxides was Fe2O3 > Cr2O3 + CaCrO4 > NiO. Overall, the pneumotoxic effects were negligible for NiO, acute but not persistent for Cr2O3 + CaCrO4, and persistent for the Fe2O3 exposures. Fe2O3, but not Cr2O3 + CaCrO4 or NiO significantly promoted lung tumors. These results provide experimental evidence that Fe2O3 is an important mediator of welding fume toxicity and support epidemiological findings and the IARC classification.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Carcinógenos/toxicidad , Compuestos Férricos/toxicidad , Neoplasias Pulmonares/inducido químicamente , Soldadura/métodos , Animales , Compuestos de Calcio/toxicidad , Carcinogénesis/inducido químicamente , Cromatos/toxicidad , Compuestos de Cromo/toxicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Neoplasias Pulmonares/patología , Masculino , Metilcolantreno/toxicidad , Ratones , Níquel/toxicidad , Acero Inoxidable/química , Acero Inoxidable/toxicidad
2.
Aquat Toxicol ; 177: 425-32, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27393920

RESUMEN

Salinization of freshwater ecosystems as a result of human activities represents a global threat for ecosystems' integrity. Whether different sources of salinity with their differing ionic compositions lead to variable effects in ecosystem functioning is unknown. Therefore, the present study assessed the impact of dryland- (50µS/cm to 11,000µS/cm) and coalmine-induced (100µS/cm to 2400µS/cm) salinization on the leaf litter breakdown, with focus on microorganisms as main decomposer, in two catchments in New South Wales, Australia. The breakdown of Eucalyptus camaldulensis leaves decreased with increasing salinity by up to a factor of three. Coalmine salinity, which is characterised by a higher share of bicarbonates, had a slightly but consistently higher breakdown rate at a given salinity relative to dryland salinity, which is characterised by ionic proportions similar to sea water. Complementary laboratory experiments supported the stimulatory impact of sodium bicarbonates on leaf breakdown when compared to sodium chloride or artificial sea salt. Furthermore, microbial inoculum from a high salinity site (11,000µS/cm) yielded lower leaf breakdown at lower salinity relative to inoculum from a low salinity site (50µS/cm). Conversely, inoculum from the high salinity site was less sensitive towards increasing salinity levels relative to inoculum from the low salinity site. The effects of the different inoculum were the same regardless of salt source (sodium bicarbonate, sodium chloride and artificial sea salt). Finally, the microorganism-mediated leaf litter breakdown was most efficient at intermediate salinity levels (≈500µS/cm). The present study thus points to severe implications of increasing salinity intensities on the ecosystem function of leaf litter breakdown, while the underlying processes need further scrutiny.


Asunto(s)
Minas de Carbón , Eucalyptus/metabolismo , Salinidad , Australia , Biomasa , Cromatos/toxicidad , Ecosistema , Ergosterol/análisis , Eucalyptus/efectos de los fármacos , Hongos/química , Hongos/efectos de los fármacos , Hongos/metabolismo , Nueva Gales del Sur , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Hojas de la Planta/microbiología , Cloruro de Sodio/toxicidad , Contaminantes Químicos del Agua/toxicidad
3.
Environ Toxicol ; 31(3): 339-49, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25270677

RESUMEN

Taraxacum officinale (L.) Weber, commonly known as Dandelion, has been widely used as a folkloric medicine for the treatment of liver and kidney disorders and some women diseases such as breast and uterus cancers. The main objective of the present study was to assess the efficiency of T. officinale leaf extract (TOE) in treating sodium dichromate hazards; it is a major environmental pollutant known for its wide toxic manifestations witch induced liver injury. TOE at a dose of 500 mg/kg b.w was orally administered once per day for 30 days consecutively, followed by 10 mg/kg b.w sodium dichromate was injected (intraperitoneal) for 10 days. Our results using Wistar rats showed that sodium dichromate significantly increased serum biochemical parameters. In the liver, it was found to induce an oxidative stress, evidenced from increase in lipid peroxidation and changes in antioxidative activities. In addition, histopathological observation revealed that sodium dichromate causes acute liver damage, necrosis of hepatocytes, as well as DNA fragmentation. Interestingly, animals that were pretreated with TOE, prior to sodium dichromate administration, showed a significant hepatoprotection, revealed by a significant reduction of sodium dichromate-induced oxidative damage for all tested markers. These finding powerfully supports that TOE was effective in the protection against sodium dichromate-induced hepatotoxicity and genotoxicity and, therefore, suggest a potential therapeutic use of this plant as an alternative medicine for patients with acute liver diseases.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cromatos/toxicidad , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Taraxacum/química , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/fisiología , Masculino , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/química , Ratas , Ratas Wistar
4.
Chemosphere ; 144: 374-81, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26383264

RESUMEN

Heavy metals such as chromium (Cr) and arsenic (As) occur in ionic form in soil, with chromate [Cr(VI)] and arsenate As(V) being the most pre-dominant forms. The application of biochar to Cr(VI) and As(V) spiked and field contaminated soils was evaluated on the reduction processes [(Cr(VI) to Cr(III)] and [As(V) to As(III))], and subsequent mobility and bioavailability of both As(V) and Cr(VI). The assays used in this study included leaching, soil microbial activity and XPS techniques. The reduction rate of As(V) was lower than that of Cr(VI) with and without biochar addition, however, supplementation with biochar enhanced the reduction process of As(V). Leaching experiments indicated Cr(VI) was more mobile than As(V). Addition of biochar reversed the effect by reducing the mobility of Cr and increasing that of As. The presence of Cr and As in both spiked and contaminated soils reduced microbial activity, but with the addition of biochar to these soils, the microbial activity increased in the Cr(VI) contaminated soils, while it was further decreased with As(V) contaminated soils. The addition of biochar was effective in mitigating Cr toxicity by reducing Cr(VI) to Cr(III). In contrast, the conversion process of As(V) to As(III) hastened by biochar was not favourable, as As(III) is more toxic in soils. Overall, the presence of functional groups on biochar promotes reduction by providing the electrons required for reduction processes to occur as determined by XPS data.


Asunto(s)
Arseniatos/metabolismo , Carbón Orgánico/química , Cromatos/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Arseniatos/toxicidad , Disponibilidad Biológica , Cromatos/toxicidad , Oxidación-Reducción , Contaminantes del Suelo/toxicidad
5.
Reprod Toxicol ; 59: 66-79, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26582256

RESUMEN

Hexavalent chromium reportedly induces reproductive toxicity and further inhibits male fertility in mammals. In this study, we investigated the molecular mechanism by which hexavalent chromium affects motility signaling in boar spermatozoa in vitro. The results indicated that Cr(VI) decreased sperm motility, protein phosphorylation, mitochondrial membrane potential (ΔΨm) and metabolic enzyme activity starting at 4µmol/mL following incubation for 1.5h. Notably, all parameters were potently inhibited by 10µmol/mL Cr, while supplementation with the dibutyryl-cAMP (dbcAMP) and the 3-isobutyl-1-methylxanthine (IBMX) prevented the inhibition of protein phosphorylation. Interestingly, high concentrations of Cr (>10µmol/mL) increased the tyrosine phosphorylation of some high-molecular-weight proteins in the principle piece but decreased that in the middle piece associated with an extreme reduction of sperm motility. These results suggest that chromium affects boar sperm motility by impairing tyrosine phosphorylation in the midpiece of sperm by blocking the cAMP/PKA pathway in boar sperm in vitro.


Asunto(s)
Cromatos/toxicidad , Cromo/toxicidad , Contaminantes Ambientales/toxicidad , Compuestos de Potasio/toxicidad , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Pieza Intermedia del Espermatozoide/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Animales , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Fosforilación , Transducción de Señal/efectos de los fármacos , Pieza Intermedia del Espermatozoide/metabolismo , Pieza Intermedia del Espermatozoide/patología , Porcinos , Tirosina
6.
Environ Toxicol Chem ; 34(8): 1841-50, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25809520

RESUMEN

Daphnia magna is a widely used model organism for aquatic toxicity testing. In the present study, the authors investigated the hydrolytic enzyme activity of D. magna after exposure to toxicant stress. In vivo enzyme activity was quantified using 15 fluorogenic enzyme probes based on 4-methylumbelliferyl or 7-amino-4-methylcoumarin. Probing D. magna enzyme activity was evaluated using short-term exposure (24-48 h) to the reference chemical K2 Cr2 O7 or the herbicide formulation Roundup®. Toxicant-induced changes in hydrolytic enzyme activity were compared with changes in mobility (International Organization for Standardization standard 6341). The results showed that hydrolytic enzyme activity was quantifiable as a combination of whole body fluorescence of D. magna and the fluorescence of the surrounding water. Exposure of D. magna to lethal and sublethal concentrations of Roundup resulted in loss of whole body enzyme activity and release of cell constituents, including enzymes and DNA. Roundup caused comparable inhibition of mobility and alkaline phosphatase activity with median effective concentration values at 20 °C of 8.7 mg active ingredient (a.i.)/L to 11.7 mg a.i./L. Inhibition of alkaline phosphatase activity by Roundup was lowest at 14 °C and greater at 20 °C and 26 °C. The results suggest that the fluorescence-based hydrolytic enzyme activity assay (FLEA assay) can be used as an index of D. magna stress. Combining enzyme activity with fluorescence measurements may be applied as a simple and quantitative supplement for toxicity testing with D. magna.


Asunto(s)
Daphnia/efectos de los fármacos , Enzimas/metabolismo , Colorantes Fluorescentes/química , Herbicidas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Fosfatasa Alcalina/metabolismo , Animales , Cromatos/toxicidad , Cumarinas/química , Daphnia/enzimología , Hidrólisis , Compuestos de Potasio/toxicidad , Pruebas de Toxicidad , Umbeliferonas/química
7.
Artículo en Inglés | MEDLINE | ID: mdl-25220772

RESUMEN

The effects of food supplementation with sodium chromate at concentrations of 1-500 µM on development of Drosophila melanogaster larvae and food intake, carbohydrate and lipid pools in adult fruit flies were investigated. Food supplementation with hexavalent chromium (Na2CrO4) at high concentrations delayed larval development and decreased the percentage of larvae that pupated which indicated a relatively low toxicity. The supplement decreased glucose levels in fly hemolymph, but at concentrations of 5-25 µM increased fly carbohydrate reserves: hemolymph trehalose and whole body trehalose and glycogen. The data on parameters of carbohydrate metabolism show that chromate possesses some insulin-mimetic properties. The changes in metabolism of carbohydrates under chromate exposure were also accompanied by an increase in total lipid levels and in the portion of triacylglycerides among all lipids. Chromate addition to fly food did not affect male or female body mass, but reduced food consumption by females at all concentrations used, whereas in males only 500 µM chromate decreased food consumption. The data show that: (1) Cr(6+) has many of the same effects as Cr(3+) suggesting that it might be just as effective to treat diabetic states, likely as a result of intracellular reduction of Cr(6+) ions, and (2) the Drosophila model can be used to develop new approaches to investigate the molecular mechanisms of chromium as an insulin-mimetic. Although it is usually believed that hexavalent chromium possesses higher toxicity than the trivalent ion, due to its easier penetration into the cell, application of hexavalent chromium may substantially decrease the chromium doses needed to get the desired effects.


Asunto(s)
Cromatos/toxicidad , Drosophila melanogaster/efectos de los fármacos , Compuestos de Sodio/toxicidad , Alimentación Animal , Animales , Metabolismo de los Hidratos de Carbono , Relación Dosis-Respuesta a Droga , Drosophila melanogaster/metabolismo , Femenino , Glucosa/metabolismo , Larva/efectos de los fármacos , Masculino , Pupa/efectos de los fármacos
8.
Biol Trace Elem Res ; 159(1-3): 304-11, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24752970

RESUMEN

Cactus (Opuntia ficus-indica) is a xerophyte plant that belongs to the Cactaceae family. The present study was designed to investigate the possible protective effects of cactus cladodes extract (CCE) on sodium dichromate-induced testis damage in adult male Wistar rats. For this purpose, CCE at a dose of 100 mg/kg was orally administrated, followed by 10 mg/kg sodium dichromate (intraperitoneal injection). After 40 days of treatment, the rats were sacrificed, and the testes were excised for histological, lipid peroxidation (LPO), and antioxidant enzyme analyses. Sodium dichromate treatment significantly (P<0.01) decreased the body, testis, and accessory sex organ weights, sperm count and motility, and serum testosterone level. In addition, histological analysis revealed pronounced morphological alterations with tubular necrosis and reduction in the number of gametes in the lumen of the seminiferous tubules of sodium dichromate-intoxicated rats. Furthermore, exposure to sodium dichromate significantly (P<0.01) increased LPO level and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in testis. Interestingly, pretreatment with CCE significantly (P<0.01) restored the serum testosterone level, sperm count, and motility to the levels of the control group. Moreover, CCE administration was capable of reducing the elevated level of LPO and significantly (P<0.01) increased SOD, CAT, and GPx activities in testis. Cactus cladodes supplementation minimized oxidative damage and reversed the impairment of spermatogenesis and testosterone production induced by sodium dichromate in the rat testis.


Asunto(s)
Cactaceae/química , Cromatos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Testículo/efectos de los fármacos , Testículo/metabolismo , Animales , Antioxidantes/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Espermatogénesis/efectos de los fármacos , Testosterona/metabolismo
9.
Biometals ; 27(3): 409-43, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24664226

RESUMEN

Occupational exposure to hexavalent chromium [Cr(VI)] has been firmly associated with the development of several pathologies, notably lung cancer. According to the current paradigm, the evolution of normal cells to a neoplastic state is accompanied by extensive metabolic reprogramming, namely at the level of energy-transducing processes. Thus, a complete understanding of the molecular basis of Cr(VI)-induced lung cancer must encompass the elucidation of the impact of Cr(VI) on metabolism. Research in this area is still in its infancy. Nonetheless, Cr(VI)-induced metabolic phenotypes are beginning to emerge. Specifically, it is now well documented that Cr(VI) exposure inhibits respiration and negatively affects the cellular energy status. Furthermore, preliminary results suggest that it also upregulates glucose uptake and lactic acid fermentation. From a mechanistic point of view, there is evidence that Cr(VI) exposure can interfere with energy transducing pathways at different levels, namely gene expression, intracellular protein levels and/or protein function. Loss of thiol redox control likely plays a key role in these processes. The transcriptional networks that control energy transduction can likewise be affected. Data also suggest that Cr(VI) exposure might compromise energy transducing processes through changes in the intracellular pools of their substrates. This article reviews, for the first time, the information available on Cr(VI) impact on mammalian cell bioenergetics. It aims to provide a framework for the understanding of the role played by bioenergetics in Cr(VI)-induced carcinogenesis and is also intended as a guide for future research efforts in this area.


Asunto(s)
Cromatos/toxicidad , Cromo/toxicidad , Metabolismo Energético/efectos de los fármacos , Neoplasias Pulmonares/inducido químicamente , Animales , Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Redes y Vías Metabólicas/efectos de los fármacos , Exposición Profesional , Estrés Oxidativo , Fenotipo
10.
BMC Pharmacol Toxicol ; 15: 15, 2014 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-24612858

RESUMEN

BACKGROUND: A convergence of technological breakthroughs in the past decade has facilitated the development of rapid screening tools for biomarkers of toxicant exposure and effect. Platforms using the whole adult organism to evaluate the genome-wide response to toxicants are especially attractive. Recent work demonstrates the feasibility of this approach in vertebrates using the experimentally robust zebrafish model. In the present study, we evaluated gene expression changes in whole adult male zebrafish following an acute 24 hr high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate concentrations corresponding to their respective 96 hr LC20, LC40 and LC60. Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal. RESULTS: Comparative analysis identified subsets of differentially expressed transcripts both overlapping and unique to each metal. Application of gene ontology (GO) and transcription factor (TF) enrichment algorithms revealed a number of key biological processes perturbed by metal poisonings and the master transcriptional regulators mediating gene expression changes. Metal poisoning differentially activated biological processes associated with ribosome biogenesis, proteosomal degradation, and p53 signaling cascades, while repressing oxygen-generating pathways associated with amino acid and lipid metabolism. Despite appreciable effects on gene regulation, nickel poisoning did not induce any morphological alterations in male zebrafish organs and tissues. Histopathological effects of cobalt remained confined to the olfactory system, while chromium targeted the gills, pharynx, and intestinal mucosa. A number of enriched transcription factors mediated the observed gene response to metal poisoning, including known targets such as p53, HIF1α, and the myc oncogene, and novel regulatory factors such as XBP1, GATA6 and HNF3ß. CONCLUSIONS: This work uses an experimentally innovative approach to capture global responses to metal poisoning and provides mechanistic insights into metal toxicity.


Asunto(s)
Cromatos/toxicidad , Cobalto/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Níquel/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Proteínas de Peces/genética , Perfilación de la Expresión Génica , Branquias/efectos de los fármacos , Branquias/patología , Intestinos/efectos de los fármacos , Intestinos/patología , Masculino , Mucosa Olfatoria/efectos de los fármacos , Mucosa Olfatoria/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Faringe/efectos de los fármacos , Faringe/patología , Pez Cebra/genética , Pez Cebra/fisiología
11.
Exp Toxicol Pathol ; 63(6): 541-8, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20494564

RESUMEN

Chromium, a major environmental pollutant, is known for its wide toxic manifestations. The present experiment pertains to the protective role of selenium (Se) against K(2)Cr(2)O(7)-induced hepatotoxicity. Female Wistar rats were divided into four groups of six each: group I served as controls which received standard diet; group II received in drinking water K(2)Cr(2)O(7) alone (700 ppm); group III received both K(2)Cr(2)O(7) and Se (0.5 Na(2)SeO(3) mg/kg of diet); group IV received Se (0.5 mg/kg of diet) for 3 weeks. Exposure of rats to chromium promoted oxidative stress with an increase in malondialdehyde (MDA) and a decrease in glutathione (GSH) levels. A decrease in glutathione peroxidase (GPx) and an increase in superoxide dismutase (SOD) and catalase (CAT) activities were observed. Se supplementation to the diet of group III improved all the parameters cited above. Yet, plasma transaminases (AST and ALT), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels increased, while high density lipoprotein-cholesterol (HDL-C) decreased. Co-administration of Se to the diet of group III restored hepatic markers to near-normal values. The biochemical results confirmed the histopathological findings. Therefore, our investigation revealed that Se was effective in preventing K(2)Cr(2)O(7)-induced hepatotoxicity.


Asunto(s)
Antioxidantes/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cromatos/toxicidad , Compuestos de Potasio/toxicidad , Selenito de Sodio/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Biomarcadores/sangre , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Femenino , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Malondialdehído/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Selenito de Sodio/administración & dosificación , Superóxido Dismutasa/metabolismo
12.
Toxicol In Vitro ; 20(4): 513-8, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16278061

RESUMEN

Evaluation of genotoxic effects of potassium chromate (K2CrO4) and cadmium chloride (CdCl2) was carried out in human blood lymphocytes in vitro as measured by the electron microscopy in situ end-labeling (EM-ISEL). EM-ISEL was used to assess DNA single-strand breaks (SSBs) expressed as number of immunogold particles per microm2 of chromatin at both chromosomal and nuclear DNA levels. Human lymphocytes were cultured in supplemented RPMI medium for 72 h including treatment for 2 h with K2CrO4 (0-150 microM), CdCl2 (0-150 microM) or methyl methanesulfonate (500 microM) as a positive control. Quantification of SSBs by EM-ISEL showed that both compounds are genotoxic agents at non-cytotoxic concentrations. This study brings new information on the utility of EM-ISEL for the evaluation of genotoxicity and confirms the genotoxic effects induced by chromium and cadmium.


Asunto(s)
Cloruro de Cadmio/toxicidad , Cromatos/toxicidad , Etiquetado Corte-Fin in Situ/métodos , Linfocitos/efectos de los fármacos , Microscopía Inmunoelectrónica/métodos , Mutágenos/toxicidad , Compuestos de Potasio/toxicidad , Adulto , Supervivencia Celular/efectos de los fármacos , Daño del ADN , ADN de Cadena Simple/efectos de los fármacos , ADN de Cadena Simple/ultraestructura , Relación Dosis-Respuesta a Droga , Humanos , Linfocitos/ultraestructura , Masculino , Microscopía Electrónica de Transmisión/métodos , Pruebas de Mutagenicidad
13.
J Ethnopharmacol ; 71(1-2): 235-40, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10904168

RESUMEN

The effect of Kombucha tea (KT) on oxidative stress induced changes in rats subjected to chromate treatment are reported. KT feeding alone did not show any significant change in malondialdehyde (MDA) and reduced glutathione (GSH) levels, but did enhance humoral response and delayed type of hypersensitivity (DTH) response appreciably over control animals. Chromate treatment significantly enhanced plasma and tissue MDA levels, decreased DTH response considerably, enhanced glutathione peroxidase and catalase activities; however, no change in GSH, superoxide dismutase and antibody titres was noticed. KT feeding completely reversed the chromate-induced changes. These results show that Kombucha tea has potent anti-oxidant and immunopotentiating activities.


Asunto(s)
Antioxidantes/farmacología , Bebidas/análisis , Cromatos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Formación de Anticuerpos/efectos de los fármacos , Cromatos/antagonistas & inhibidores , Eritrocitos/inmunología , Fermentación , Glutatión/sangre , Hipersensibilidad Tardía/inmunología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/sangre , Ratas , Ratas Sprague-Dawley
14.
Biometals ; 11(2): 101-6, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9542063

RESUMEN

The responses of Saccharomyces cerevisiae towards the oxyanions tellurite, selenite and chromate were investigated in order to establish the involvement of the yeast vacuole in their detoxification. Three mutants of S. cerevisiae with defective vacuolar morphology and function were used; mutant JSR180 delta 1 is devoid of any vacuolar-like structure while ScVatB and ScVatC are deficient in specific protein subunits of the vacuolar (V)-H(+)-ATPase. All the mutant strains showed increased sensitivity to tellurite and chromate compared to their parental strains. Such sensitivity of the mutants was associated with increased accumulation of tellurium and chromium. These results indicate that accumulation of both tellurium and chromium occurred mainly in the cytosolic compartment of the cell, with detoxification influenced by the presence of a functionally-active vacuole which may play a role in compartmentation as well as regulation of the cytosolic compartment for optimal expression of a detoxification mechanism, e.g. reduction. In contrast, the vacuolar-lacking mutant, JSR180 delta 1, and the defective V-H+ATPase mutant ScVatB displayed lower selenium accumulation than their parental strains. Additionally, the mutant strain ScVatB displayed a higher tolerance to selenite than the parental strain. This result suggests that accumulation of selenium occurs mainly in the vacuolar compartment of the cell with tolerance depending on the ability of the cytosolic component to reduce selenite to elemental selenium, which might, in turn, be related to activity of the V-H(+)-ATPase. These results are discussed in relation to vacuolar compartmentation and the significance of the vacuolar H(+)-ATPase in cytosolic homeostasis of H+ both of which may affect the accumulation, reduction, and tolerance to the tested metal(loids).


Asunto(s)
Metales/toxicidad , Mutación , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , ATPasas de Translocación de Protón Vacuolares , Vacuolas/genética , Vacuolas/metabolismo , Cromatos/toxicidad , Cromo/farmacocinética , Farmacorresistencia Microbiana/genética , Inactivación Metabólica , Metales/farmacocinética , ATPasas de Translocación de Protón/metabolismo , Saccharomyces cerevisiae/metabolismo , Selenio/farmacocinética , Selenito de Sodio/toxicidad , Telurio/farmacocinética , Telurio/toxicidad
15.
Toxicol Appl Pharmacol ; 146(2): 270-80, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9344895

RESUMEN

Certain hexavalent chromium compounds are documented human carcinogens. Exposure of cells to particulate forms of chromium results in cell-enhanced dissolution of particles in the extracellular microenvironment and chronic production of chromium oxyanions, which are taken up by the cell through an anion transport system and are genotoxic and clastogenic. It was previously shown that apoptosis is the mode of cell death of nearly all of the Chinese hamster ovary cells (CHO-AA8 cell line), which die after high-dose, short-term treatments with soluble sodium chromate. In this report the mode of cell killing by particulate lead chromate and of low-dose continuous treaments of soluble sodium chromate designed to mimic conditions of ionic chromate uptake after lead chromate exposure was examined. CHO-AA8 cells were treated for 24 hr with doses of sodium chromate or lead chromate which cause a 50% decrease in survival in colony-forming effeciency assays. Longer treatments (up to 72 hr) at the same doses did not decrease survival further than the 24-hr exposure. Morphological changes indicative of apoptosis, as well as internucleosomal DNA fragmentation, were detectable by 24 hr after treatment with lead chromate or soluble sodium chromate. All of the cells killed by treatments with lead chromate particles underwent apoptosis as the mode of cell death and this was accurately modeled in cell culture by continuous treatments with low-dose soluble sodium chromate. Exposure of cells to hexavalent chromium compounds causes a spectrum of DNA damage which can be selectively altered by pretreatment of cells with antioxidant vitamins prior to chromium exposure. Here we show that ascorbate and alpha-tocopherol markedly inhibited the chromosomal aberrations induced by both particulate and soluble chromate compounds, even though chromium adduct levels were not decreased by either vitamin pretreatment. Cell survival assays showed that ascorbate, but not alpha-tocopherol, protected cells from apoptosis induced by sodium chromate. The results differentiate chromium-induced apoptosis from both chromosomal damage and adduct levels and suggest that other lesions sensitive to ascorbate but not tocopherol are the proximal inducing signal for chromium-induced apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Ácido Ascórbico/farmacología , Cromatos/toxicidad , Daño del ADN , Plomo/toxicidad , Vitamina E/farmacología , Animales , Apoptosis/genética , Células CHO/efectos de los fármacos , Células CHO/patología , Células CHO/ultraestructura , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Colorantes/toxicidad , Cricetinae , Aductos de ADN/análisis , Fragmentación del ADN/efectos de los fármacos , Microscopía Electrónica , Microscopía Fluorescente , Tamaño de la Partícula
16.
Carcinogenesis ; 13(11): 2113-20, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1330350

RESUMEN

In order to understand the possible role of reactive intermediates in the formation of tissue-specific DNA damage by chromium(VI), electron paramagnetic resonance spectroscopy was used to study the in vivo formation of chromium(V) in the liver and red blood cells of 14 day chick embryos following treatment with chromium(VI). In vivo administration of sodium dichromate onto the inner shell membrane of 14 day chick embryos resulted in the formation of a persistent chromium(V) species in liver cells (g = 1.987). The intensity of the chromium(V) signal in liver cells plateaued at 70 min and persisted for 240 min after treatment with chromium(VI). The dependence of chromium(V) formation on the dose of sodium dichromate administered to the embryo was clearly different in liver versus red blood cells. Chromium(V) was detected in red blood cells only at high doses of sodium dichromate (0.50-0.60 mmol/kg), whereas chromium(V) was undetectable in red blood cells at lower doses of sodium dichromate (0.10-0.30 mmol/kg) which produced clear evidence for chromium(V) in liver. Uptake studies showed that total chromium levels in red blood cells were 10-fold greater than in liver cells, and that up to 10% of the total chromium existed as chromium(V) in liver and red blood cells in vivo. Depletion of glutathione by pretreatment of embryos with L-buthionine-S,R-sulfoximine (BSO) for 24 h prior to treatment with a high dose of sodium dichromate (0.60 mmol/kg) caused both a decrease in the levels of chromium(V) species produced and a decrease of chromium uptake into red blood cells 50 min after treatment. At this high dose of chromium(VI), BSO pre-treatment had no effect on the level of the chromium(V) or on chromium uptake into liver cells after a 70 min incubation period. Thus, the concentration of chromium(V) inside the cell correlated with the levels of chromium taken up into the cell. Chromium(V) may be the form of chromium which is responsible for induction of DNA damage following in vivo administration of sodium dichromate.


Asunto(s)
Cromo/metabolismo , Eritrocitos/metabolismo , Hígado/metabolismo , Animales , Antimetabolitos/farmacología , Butionina Sulfoximina , Células Cultivadas , Embrión de Pollo , Cromatos/toxicidad , Espectroscopía de Resonancia por Spin del Electrón , Eritrocitos/efectos de los fármacos , Glutatión/metabolismo , Cinética , Hígado/citología , Hígado/efectos de los fármacos , Hígado/embriología , Metionina Sulfoximina/análogos & derivados , Metionina Sulfoximina/farmacología
17.
Artículo en Inglés | MEDLINE | ID: mdl-2567222

RESUMEN

1. The intraperitoneal treatment of adult male Wistar rats with various combinations of low doses of sodium dichromate (5 mg/kg), sodium arsenate (25 mg/kg) and copper sulphate (5.9 mg/kg) tended to counteract the inherent acute toxicity of each compound. 2. The co-administration of low doses of one or more of the test compounds with a high dose of sodium dichromate (35 mg/kg), sodium arsenate (90 mg/kg) or copper sulphate (23.5 mg/kg) resulted in a significant increase in acute toxicity in comparison with that produced by the administration of high doses of dichromate, arsenate or Cu2+ alone.


Asunto(s)
Arseniatos/toxicidad , Arsénico/toxicidad , Cromatos/toxicidad , Cobre/toxicidad , Animales , Arseniatos/administración & dosificación , Peso Corporal/efectos de los fármacos , Cromatos/administración & dosificación , Cobre/administración & dosificación , Sulfato de Cobre , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Riñón/efectos de los fármacos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas
18.
Cancer Lett ; 38(1-2): 1-7, 1987 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-3690500

RESUMEN

The effects of vitamin E, vitamin B2 and selenite on DNA single strand breaks induced by Na2CrO4 were examined by alkaline elution. Incubation of Chinese hamster V-79 cells with alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure to Na2CrO4 resulted in a decrease of DNA breaks produced by this compound. However, similar pretreatment with riboflavin (vitamin B2) or Na2SeO3 resulted in an enhanced formation of breaks induced by Na2CrO4. Pretreatment with Na2SeO3 resulted in increased levels of glutathione in these cells while levels of glutathione remained the same with vitamin E or vitamin B2. These results suggest that Na2CrO4 induced DNA breaks appear to be mediated by the formation of free radicals and/or cellular reductive metabolism.


Asunto(s)
Cromatos/toxicidad , Daño del ADN , Riboflavina/farmacología , Selenio/farmacología , Compuestos de Sodio , Vitamina E/farmacología , Animales , Células Cultivadas , Cricetinae , Radicales Libres , Glutatión/análisis , Ácido Selenioso
19.
J Steroid Biochem ; 27(4-6): 1035-41, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-2826897

RESUMEN

Following lung instillation in adult male rats of 3.4 mumol hexavalent chromium (K2Cr2O7) dissolved in 0.5 ml of 0.9% NaCl, increased levels of lung surfactant could be detected after 48 h. The blood serum concentration of corticosterone was elevated in these animals. Blood serum thyroxine and triiodothyronine showed an initial increase after lung instillation of hexavalent chromium followed by a decline. Metabolism of testosterone by the alveolar macrophages to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol was reduced 6 and 12 h after the K2Cr2O7 instillation, which was also associated with damage of lung cell function and decreased uptake by the alveolar macrophages of Candida albicans particles. As early as 12 h after s.c. administration of 400 micrograms dexamethasone/100 g body wt, increased levels of lung surfactant could be measured. At this time the lungs showed no signs of cellular damage, and metabolism of testosterone as well as uptake of Candida albicans particles by the alveolar macrophages were normal. Lower s.c. doses of dexamethasone did not result in raising the levels of lung surfactant in 12 h. Within 12 h after s.c. administration of large doses of testosterone, dihydrotestosterone or dehydroepiandrosterone no measurable effects on the levels of lung surfactant could be measured. Since animals treated with dexamethasone (200 micrograms/100 g body wt) or long-acting synthetic ACTH (100 micrograms i.m. Synacthen Depot/100 g body wt) for 5 days after lung instillation of K2Cr2O7 had extremely high levels of lung surfactant, it is concluded that the corticosteroids in adult rats may help to create augmented surfactant levels following lung intoxication. This could proceed via stimulation of surfactant production and reduction of surfactant removal. Different aspects of lung surfactant metabolism are discussed.


Asunto(s)
Corticoesteroides/sangre , Cromatos/toxicidad , Enfermedades Pulmonares/metabolismo , Pulmón/metabolismo , Compuestos de Potasio , Surfactantes Pulmonares/metabolismo , Hormona Adrenocorticotrópica/farmacología , Animales , Cromatos/farmacología , Dexametasona/farmacología , Pulmón/efectos de los fármacos , Enfermedades Pulmonares/inducido químicamente , Macrófagos/metabolismo , Masculino , Alveolos Pulmonares/metabolismo , Ratas , Ratas Endogámicas , Testosterona/metabolismo
20.
Toxicol Appl Pharmacol ; 83(1): 142-7, 1986 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-3952743

RESUMEN

The usefulness of N-acetylcysteine (NAC) as a chelating agent was studied for the toxin potassium dichromate, lead tetraacetate, and boric acid. Mature Sprague-Dawley rats were intoxicated with these substances and placed in metabolic cages. Urinary excretion rates of intoxicant and total urine volume were determined during treatment with N-acetylcysteine, calcium EDTA, and/or dimercaptosuccinic acid, N-acetylcysteine proved to be the most effective agent at increasing the excretion of chromium and boron and was also able to reverse the oliguria associated with these toxins. Dimercaptosuccinic acid was most effective at the chelation of lead. NAC did not increase the excretion of lead. We conclude that NAC may be useful in intoxications due to chromate and borate and is effective at reversing the oliguria associated with these intoxicants.


Asunto(s)
Acetilcisteína/uso terapéutico , Ácidos Bóricos/toxicidad , Quelantes/uso terapéutico , Cromatos/toxicidad , Intoxicación por Plomo/tratamiento farmacológico , Plomo/toxicidad , Compuestos Organometálicos , Dicromato de Potasio/toxicidad , Animales , Ácidos Bóricos/orina , Cromo/orina , Femenino , Cinética , Plomo/orina , Masculino , Ratas , Ratas Endogámicas , Factores de Tiempo
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