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F Díaz-Barriga

Publications and source records attributed to F Díaz-Barriga.

17 recordsLinked to original sources

Effect of arsenic, cadmium and lead on the induction of apoptosis of normal human mononuclear cells.

The aim of this work was to investigate the effect of cadmium, lead and arsenic on the apoptosis of human immune cells. Peripheral blood mononuclear cells (MNC) were incubated with increasing concentrations of these metals and then cellular apoptosis was determined by flow cytometry and by DNA electrophoresis. We found that arsenic induced a significant level of apoptosis at 15 microM after 48h of incubation. Cadmium had a similar effect, but at higher concentrations (65 microM). In addition, cadmium exerted a cytotoxic effect on MNC that seemed to be independent of the induction of apoptosis. In contrast, concentrations of lead as high as 500 microM were nontoxic and did not induce a significant degree of apoptosis. Additional experiments showed that arsenic at concentrations as low as 1.0 microM had a significant pro-apoptotic effect when cells were cultured in the presence of this pollutant for more than 72. Non-T cells were more susceptible than T lymphocytes to the effect of arsenic and cadmium. Interestingly, MNC from children chronically exposed to arsenic showed a high basal rate of apoptosis and a diminished in vitro sensibility to this metalloid. Our results indicate that both arsenic and cadmium are able to induce apoptosis of lymphoid cells, and suggest that this phenomenon may contribute to their immunotoxic effect in vivo.

Adult↗

Exposure to arsenic and lead and neuropsychological development in Mexican children.

This cross-sectional study examined the effects of chronic exposure to lead (Pb), arsenic (AS) and undernutrition on the neuropsychological development of children. Two populations chronically exposed to either high (41 children) or low (39 children) levels of As and Pb were analyzed using the Wechsler Intelligence Scale for Children, Revised Version, for México (WISC-RM). Geometric means of urinary arsenic (AsU) and lead in blood (PbB) were 62.9+/-0.03 (microgAs/g creatinine) and 8.9+/-0.03 (microg/dl) for the exposed group and 40.2+/-0.03 (microgAs/g creatinine) and 9.7+/-0.02 (microg/dl) for the reference group. The height for age index (HAI) was used as an indicator of chronic malnutrition and sociodemographic information was obtained with a questionnaire. Lead and arsenic were measured by atomic absorption spectrophotometry. Data on full, verbal, and performance intelligence quotients (IQ) scores, long-term memory, linguistic abstraction, attention span, and visuospatial organization were obtained through the WISC-RM. After controlling for significant potential confounders verbal IQ (P<0.01) decreased with increasing concentrations of AsU. The HAI correlated positively with full-scale and performance IQ (P<0.01). Higher levels of AsU were significantly related to poorer performance on WISC-RM factors examining long-term memory and linguistic abstraction, while lower scores in WISC-RM factors measuring attention were obtained at increasing values of PbB. Our results suggest that exposure to As and chronic malnutrition could have an influence on verbal abilities and long-term memory, while Pb exposure could affect the attention process even at low levels.

Arsenic↗

Induction of genotoxicity by cadmium chloride inhalation in several organs of CD-1 mice.

In recent years, the concentration of metals in the environment has increased significantly. Metal compounds, as a group, are among the best-documented human carcinogens, but the mechanisms by which they act are not completely understood. In the present study a cadmium inhalation model in mice was implemented in order to detect the induction of genotoxic damage as single-strand breaks and alkali-labile sites in several organs (nasal epithelial cells, lung, whole blood, liver, kidney, bone marrow, brain and testicle) using the single cell gel electrophoresis (SCGE) or Comet assay. We found differences among the studied organs after a single and subsequent inhalations: in the organs analyzed we observed that major DNA damage was induced after a single inhalation; in subsequent inhalations there was a tendency to maintain the same magnitude of damage or in some cases it decreased. A correlation between length of exposure, DNA damage and metal tissue concentration was found. These results suggest that cadmium chloride inhalation induces systemic DNA damage; some organs showed less damage than others (liver, brain, etc.) and this finding could be as a consequence of the capacity to remove the damage induced by long periods of exposure, possibly because of the induction of detoxifying mechanisms such as induction of metallothionein.

Administration, Inhalation↗

The application of single cell gel electrophoresis or Comet assay to human monitoring studies.

OBJECTIVE: In the search of new human genotoxic biomarkers, the single cell gel electrophoresis assay has been proposed as a sensible alternative. MATERIAL AND METHODS: This technique detects principally single strand breaks as well as alkali-labile and repair-retarded sites. RESULTS: Herein we present our experience using the single cell gel electrophoresis assay in human population studies, both occupationally and environmentally exposed. CONCLUSIONS: We discuss the assay feasibility as a genotoxic biomarker.

Biomarkers↗

[A method for assessing health risks in mining sites].

OBJECTIVE: Considering the health risk associated with mining areas, in this work a methodology for the health assessment of this kind of hazardous sites is proposed. MATERIAL AND METHODS: The methodology includes a toxicological assessment, an environmental monitoring of metals, and the exposure assessment of the high risk population. The scheme was evaluated in the mining area of Villa de la Paz, San Luis Potosi, Mexico. The toxicological studies were done in rats treated with mining waste, biomarkers of effect for liver and central nervous tissue were analyzed. Metals levels in surface soil, household dust and water were studied. Finally, urinary arsenic was quantified in children. RESULTS: Neurotoxicity and hepatotoxicity of the mining waste were shown in rats. Then, arsenic and lead levels were analyzed in surface soil, household dust, and water. In all three media, exposure points, heavily contaminated with both metals, were localized. Finally, high levels of urinary arsenic were found in children living in the vicinity of the mine. CONCLUSIONS: Taking into account all these results, the Mexican authorities concluded that a high health risk is present in Villa de la Paz, and a remediation program is in progress.

Animals↗

Effects of oral exposure to mining waste on in vivo dopamine release from rat striatum.

Several single components of mining waste (arsenic, manganese, lead, cadmium) to which humans are exposed at the mining area of Villa de la Paz, Mexico, are known to provoke alterations of striatal dopaminergic parameters. In this study we used an animal model to examine neurochemical changes resulting from exposure to a metal mixture. We used microdialysis to compare in vivo dopamine release from adult rats subchronically exposed to a mining waste by oral route with those from a control group and from a sodium arsenite group (25 mg/kg/day). We found that arsenic and manganese do accumulate in rat brain after 2 weeks of oral exposure. The mining waste group showed significantly decreased basal levels of dihydroxyphenylacetic acid (DOPAC; 66.7 +/- 7.53 pg/ microl) when compared to a control group (113.7 +/- 14.3 pg/ microl). Although basal dopamine release rates were comparable among groups, when the system was challenged with a long-standing depolarization through high-potassium perfusion, animals exposed to mining waste were not able to sustain an increased dopamine release in response to depolarization (mining waste group 5.5 +/- 0.5 pg/ microl versus control group 21.7 +/- 5.8 pg/ microl). Also, DOPAC and homovanillic acid levels were significantly lower in exposed animals than in controls during stimulation with high potassium. The arsenite group showed a similar tendency to that from the mining waste group. In vivo microdialysis provides relevant data about the effects of a chemical mixture. Our results indicate that this mining waste may represent a health risk for the exposed population.

Administration, Oral↗

The El Paso smelter 20 years later: residual impact on Mexican children.

Although there has been considerable concern regarding cross-border industrial contamination between Mexico and the United States, there are remarkably few data. One notable case study is the smelter in El Paso, Texas. In 1974 blood lead levels higher than 40 micrograms/dl were detected in 52% of children studied near the smelter, in the adjacent Mexican community of Anapra in Ciudad Juarez, Chihuahua. Lead smelting at this plant was halted in 1985, and as a result, lead levels in air decreased sharply; consequently, children's exposure to lead and other metals should have diminished accordingly. In order to assess the effect of removal of lead emissions from the area, three geographical locations in Anapra, varying in distance from the smelter source, were evaluated for lead, arsenic, and cadmium levels in soil and for lead in blood of children. It was found that lead levels in soil were inversely correlated with distance from the smelter. Arsenic and cadmium levels in soil were constant among the three sectors. However, at residential sites closer to the smelter, a higher percentage of children was found with blood lead levels exceeding the Centers for Disease Control's action level of 10.0 micrograms/dl. In the sector closest to the border 43% of children had blood lead levels greater than 10.0 micrograms/dl. Although blood lead levels in children living in Anapra have dropped approximately fourfold in 20 years, our results indicate a moderate continued risk of lead exposure. This study demonstrates the persistent impact that may result from cross-border contamination and raises provocative questions regarding appropriate action and the responsibility for financing such action.

Air Pollutants↗

Acute toxicological effects in rats treated with a mixture of commercially formulated products containing methyl parathion and permethrin.

The study examined the interactions between a commercial formulation of methyl parathion (CF-MP) and a commercially formulated product of permethrin (CF-PMT) in male rats. The acute toxicity (LD50 values) and brain cholinesterase activity were investigated as toxicological endpoints. Results indicated that CF-MP modified the acute toxicity of CF-PMT. When animals were treated with a mixture, the addition of 380 mg/kg of CF-MP reduced the LD50 of CF-PMT by only 9.0%; however, when rats received CF-MP at 464 mg/kg, the LD50 of CF-PMT was reduced by 37% (P < 0.001). Also, CF-PMT decreased the CF-MP-induced inhibition of cholinesterase activity by 50% (P < 0.05). It was interesting to observe that xylene, which is the most abundant component in the vehicle of both formulations, had no effect on the CF-MP-induced inhibition of the cholinesterase activity. There was no relation between lethality and the inhibition of the brain cholinesterase activity in rats treated with mixtures containing CF-MP+CF-PMT or with either commercially formulated product alone. Considering the increased toxicity observed in rats treated with CF-PMT+CF-MP, it would be advisable to investigate further the interactions between both pesticides.

Animals↗

Endemic fluorosis in San Luis Potosi, Mexico. I. Identification of risk factors associated with human exposure to fluoride.

In order to identify risk factors associated with human exposure to fluoride in San Luis Potosi (SLP), Mexico, a biochemical and epidemiological study was carried out in 1992. Results from the analysis of fluoride sources showed that 61% of tap water samples had fluoride levels above the optimal level of 0.7-1.2 ppm. The levels were higher after boiling. In bottled water, fluoride levels ranged from 0.33 to 6.97 ppm. These sources are important since in SLP 82% of the children drink tap water, 31% also drink bottled water, 92% prepare their food with tap water, 44% boiled all the drinking water, and 91% used infant formula reconstituted with boiled water. The prevalence and severity of dental fluorosis in children (11-13 years old) increased as the concentration of water fluoride increased. At levels of fluoride in water lower than 0.7 ppm a prevalence of 69% was found for total dental fluorosis, whereas at levels of fluoride in water higher than 2.0 ppm a prevalence of 98% was found. In the same children, fluoride levels in urine were quantified. The levels increased as the concentration of water fluoride increased. Regressional analysis showed an increment of 0.54 ppm (P < 0.0001) of fluoride in urine for each ppm of fluoride in water. Fluoride urinary levels were higher in samples collected during the afternoon (1800) when compared with sample collected during the morning (1100). Taking together all these results, three risk factors for human exposure to fluoride in SLP can be identified: ambient temperature, boiled water, and food preparation with boiled water. These factors explain the prevalence of dental fluorosis in SLP.

Adolescent↗

Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of glutathione levels.

The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels, but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart.

Acetylcysteine↗

Toxicological assessment of azarcon, a lead salt used as a folk remedy in Mexico. I. Oral toxicity in rats.

Azarcon, a lead tetroxide salt, is used among Mexican and Mexican-American populations for the treatment of digestive illness. Chemical analysis of the azarcon sample used in this study showed it to be 96% lead, 1% calcium, 1% other minor metals, and 2% unidentified material. Taking into account the fact that Pb absorption was estimated at 2% following a single oral administration of 100 mg/kg (Aungst et al., 1981), it is possible to propose a chemical interaction between the components of azarcon, and as a result, the toxicity of Pb tetroxide would be different when given as azarcon than when given as a pure compound. The present work studied this possibility, with the following results. When the treatments of equal doses of pure Pb tetroxide and azarcon were compared (158 mg/kg/day p.o. for 96 h), five of nine tissues studied had similar Pb concentrations. However, with the pure compound the Pb levels were higher in bone and intestines; while with azarcon the Pb levels were higher in heart and brain. The pure Pb tetroxide treatment affects lipid peroxidation only in liver, but a low induction of peroxidation was found also in kidney and heart in rats which received the azarcon treatment. Liver and kidney damage were evident in rats treated with a high dose of azarcon (1.1 g/kg/day p.o. for 96 h), while the effects with the pure compound were similar in type but lower in magnitude. Pb tetroxide as a pure compound inhibits ALA-D by 26% while an inhibition of 42% was found with azarcon.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosí, Mexico.

The main purpose of this study was to assess environmental contamination by arsenic and cadmium in a smelter community (San Luis Potosí City, México) and its possible contribution to an increased body burden of these elements in children. Arsenic and cadmium were found in the environment (air, soil, and household dust, and tap water) as well as in the urine and hair from children. The study was undertaken in three zones: Morales, an urban area close to the smelter complex; Graciano, an urban area 7 km away from the complex; and Mexquitic, a small rural town 25 km away. The environmental study showed that Morales is the most contaminated of the zones studied. The range of arsenic levels in soil (117-1396 ppm), dust (515-2625 ppm), and air (0.13-1.45 micrograms/m3) in the exposed area (Morales) was higher than those in the control areas. Cadmium concentrations were also higher in Morales. Estimates of the arsenic ingestion rate in Morales (1.0-19.8 micrograms/kg/day) were equal to or higher than the reference dose of 1 microgram/kg/day calculated by the Environmental Protection Agency. The range of arsenic levels in urine (69-594 micrograms/g creatinine) and hair (1.4-57.3 micrograms/g) and that of cadmium in hair (0.25-3.5 micrograms/g) indicated that environmental exposure has resulted in an increased body burden of these elements in children, suggesting that children living in Morales are at high risk of suffering adverse health effects if exposure continues.

Air Pollutants↗

Biological monitoring of workers at a recently opened hazardous waste disposal site.

A health assessment was performed in a recently opened landfill for toxic waste. The site has received 14,000 tons of hazardous waste, confined in drums or deposited as bulk material, which were left outdoors for seven months. The analysis in some samples showed that the waste is rich in heavy metals, however we did not find high levels of contaminates in air or surface soil in different areas on-site. When compared to a control group, high-risk workers show higher levels of arsenic in urine and hair, and non-specific symptoms (irritability and insomnia). But among groups, we did not find statistical differences in urinary mercury, blood lead, phenol in urine, cadmium in hair or blood, sister chromatid exchange values, lymphocytes proliferation kinetics, liver function tests, and other non-specific symptoms. We considered this project as a background study for human exposure to hazardous waste, providing useful results for the future evaluation of chronic effects in the same population.

Adult↗

Arsenic-cadmium interaction in rats: toxic effects in the heart and tissue metal shifts.

Previously, we had shown that arsenic interacts with cadmium in rats; our results showed that the toxicity of a mixture of arsenic + cadmium cannot be predicted by the toxic mechanisms of the individual components. In this paper, we present further evidence about the interaction of arsenic and cadmium in rats. The results were: arsenic modified the 24 h-LD50 value of cadmium more clearly than cadmium did with the one of arsenic; based on the LD50 values, the mixtures we studied were more toxic than either metal alone. With single doses (As 10 mg/kg, Cd 2.6 mg/kg, and As 10 mg/kg + Cd 2.6 mg/kg) the mixture As + Cd was more toxic than each metal. At these doses, cadmium significantly induces the levels of glutathione, metallothionein, and lipid peroxidation in heart tissue, as compared to a saline group of rats. Arsenic incremented glutathione and lipid peroxidation at higher values than those obtained with cadmium. The mixture of As + Cd behaved as arsenic in the induction of lipid peroxidation and glutathione and like cadmium in metallothionein induction. Finally, rats treated with As + Cd had less Cd in liver than animals treated only with cadmium, and more As in heart tissue than rats treated only with arsenic. Our results give further evidence about the arsenic-cadmium interaction in rats, demonstrate the utility of employing different biomarkers in the study of chemical mixtures and indicate that heart tissue is affected not only by the mixture of As + Cd, but also by either metal alone.

Animals↗

Arsenic-cadmium interaction in rats.

Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone.

Animals↗

Purification and characterization of GP-55, a protein associated with actin-based cytoplasmic gels derived from brain tissue.

Incubation of rat brain cytoplasmic extracts results in the formation of three-dimensional gels that can be collapsed by low-speed centrifugation. Electrophoresis in polyacrylamide gels indicate that these cytoplasmic gels are composed of actin and several associated proteins. Among the latter we have identified a component with an apparent molecular mass of 55,000 daltons. The results of two-dimensional electrophoresis, peptide mapping, and in vivo labeling experiments with [35S]methionine, indicate that the 55-kDa protein is composed of two different gene products we have named alpha and beta; a third polypeptide, named beta', probably derives from the beta polypeptide as a result of some posttranslational modification(s). These three polypeptides, which have the same molecular weight but different isoelectric points, are present in a rather pure preparation of the 55-kDa protein, obtained from cytoplasmic gels by ion-exchange chromatography. In vitro, purified 55-kDa protein interacts in a specific manner with F-actin, as shown by viscosimetry and electron microscopy, leading to the formation of a complex network of cross-linked microfilament bundles. The results of immunofluorescence experiments indicate that the 55-kDa protein is located intracellularly in structures belonging to the Golgi apparatus, and that it is not only present in every type of rat cell tested but also in primary cultures of chick embryo neurons. Based on its intracellular location, we have named the 55-kDa protein as Golgi Protein-55 (GP-55).

Actins↗

Effects of lead-arsenic combined exposure on central monoaminergic systems.

Lead acetate (116 mg/kg/day), arsenic (11 or 13.8 mg/kg/day as sodium arsenite), a lead-arsenic mixture or vehicle were administered to adult mice through gastric intubation during 14 days. Then, the regional content of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4 dihydroxyphenyl-acetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HIAA), arsenic, and lead were quantified. Compared with the accumulation after single element exposures, the mixture elicited a higher accumulation of lead and a lower arsenic accumulation in the brain. Compared to controls, lead induced only an augmentation of DOPAC (200%) in the hypothalamus. By contrast, the mixture provoked increases of DOPAC in the hypothalamus (250%), DA and 5-HIAA in the striatum (67 and 187%, respectively) and NE decreased in the hypothalamus (45%). Although these alterations were similar to those produced by arsenic alone, the mixture provoked a 38% decrease of NE in the hippocampus and increases of 5-HT in midbrain and frontal cortex (100 and 90%, respectively) over control values, alterations that were not elicited by either metal alone. These results demonstrate an interaction arsenic/lead on the central monoaminergic systems of the adult mouse.

3,4-Dihydroxyphenylacetic Acid↗