Lourdes Ballinas-Casarrubias

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico

Background Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. Objective This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. Methods We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. Results After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Conclusions Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Citation Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742

Associations between Arsenic Species in Exfoliated Urothelial Cells and Prevalence of Diabetes among Residents of Chihuahua, Mexico

Background: A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals. Objectives: Our goal was to examine associations between the prevalence of diabetes and concentrations of As species in exfoliated urothelial cells (EUC) as an alternative to the measures of As in urine. Methods: We measured concentrations of trivalent and pentavalent iAs methyl-As (MAs) and dimethyl-As (DMAs) species in EUC from 374 residents of Chihuahua, Mexico, who were exposed to iAs in drinking water. We used fasting plasma glucose, glucose tolerance tests, and self-reported diabetes diagnoses or medication to identify diabetic participants. Associations between As species in EUC and diabetes were estimated using logistic and linear regression, adjusting for age, sex, and body mass index. Results: Interquartile-range increases in trivalent, but not pentavalent, As species in EUC were positively and significantly associated with diabetes, with ORs of 1.57 (95% CI: 1.19, 2.07) for iAsIII, 1.63 (1.24, 2.15) for MAsIII, and 1.31 (0.96, 1.84) for DMAsIII. DMAs/MAs and DMAs/iAs ratios were negatively associated with diabetes (OR = 0.62; 95% CI: 0.47, 0.83 and OR = 0.72; 95% CI: 0.55, 0.96, respectively). Conclusions: Our data suggest that uncertainties associated with measures of As species in urine may be avoided by using As species in EUC as markers of iAs exposure and metabolism. Our results provide additional support to previous findings suggesting that trivalent As species may be responsible for associations between diabetes and chronic iAs exposure. Citation: Currier JM, Ishida MC, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Gutiérrez-Torres DS, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Del Razo LM, García-Vargas GG, Saunders RJ, Drobná Z, Fry RC, Matoušek T, Buse JB, Mendez MA, Loomis D, Stýblo M. 2014. Associations between arsenic species in exfoliated urothelial cells and prevalence of diabetes among residents of Chihuahua, Mexico. Environ Health Perspect 122:1088–1094; http://dx.doi.org/10.1289/ehp.1307756

A Concurrent Exposure to Arsenic and Fluoride from Drinking Water in Chihuahua, Mexico

Inorganic arsenic (iAs) and fluoride (F−) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F− in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F− concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F−/L. Urinary arsenic (U-tAs) and urinary F− (U-F−) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F−/mL. A strong positive correlation was found between iAs and F− concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F− concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F−, raising questions about possible contribution of F− exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F− exposures and its related health risks deserves immediate attention.

Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico

Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure.

Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to myriad adverse health effects, including cancer of the bladder. We set out to identify DNA methylation patterns associated with arsenic and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total arsenic and arsenic species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 arsenic-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the arsenic- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer.

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism-and perhaps with susceptibility to iAs-associated disease-may vary in settings with exposure level.

Identification of the GST-T1 and GST-M1 Null Genotypes Using High Resolution Melting Analysis

Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and β-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an automated workflow as a simple, sensitive, and time and money saving procedure for rapid identification of the GST-T1 and GST-M1 positive or null genotypes.

Levels and Distribution of Pollutants in the Waters of an Aquatic Ecosystem in Northern Mexico

The availability of good quality water resources is essential to ensure healthy crops and livestock. The objective of this study was to evaluate the level of pollution in Bustillos Lagoon in northern Mexico. Physical-chemical parameters like sodium, chloride, sulfate, electrical conductivity, nitrates, and the pesticide dichlorodiphenyltrichloroethane (DDT) were analyzed to determine the water quality available in the lagoon. Although DDT has been banned in several countries, it is still used for agricultural purposes in Mexico and its presence in this area had not been analyzed previously. Bustillos Lagoon was divided into three zones for the evaluation: (1) industrial; (2) communal lands; and (3) agricultural. The highest concentrations of sodium (2360 mg/L) and SAR (41 meq/L) reported in the industrial zone are values exceeding the United Nations Food and Agricultural Organization (FAO) irrigation water quality guidelines. DDT and its metabolites were detected in all of the 21 sites analyzed, in the agricultural zone ∑DDTs = 2804 ng/mL, this level is much higher than those reported for other water bodies in Mexico and around the world where DDT has been used heavily. The water in the communal zone is the least contaminated, but can only be recommended for irrigation of plants with high stress tolerance and not for crops.

Biopolymers from Waste Biomass — Extraction, Modification and Ulterior Uses

The residues coming from woodlands and agricultural exploitation constitute the most abundant biomass available on earth. Its importance as a source of renewable energy has grown in addition to the environmental impact. Biomass waste is a lignocellulosic feedstock which contains three main biopolymers: cellulose, hemicel‐ lulose and lignin. It could be utilized for the production of a number of value-added products due to their chemical composition, but it is necessary to efficiently recover the valuable biopolymer as intact as possible by different processing techniques.For different applications, the principal objective of pre-treatment is to keep the cellu‐ lose intact, meanwhile hemicellulose and lignin are removed. The yields of the frac‐ tions depend on the pre-treatment method, which is the most expensive step in biomass conversion. Traditionally, cellulose is obtained by kraft, sulphite and soda treatments. These methods are non-environmentally friendly and generate huge quantities of toxic wastes. Recently developed models considering the environmen‐ tal laws encourage the sustainable processing of biomass into value-added prod‐ ucts. The use of ionic liquids as new solvents for biomass waste and organosolv processes is reviewed, which are used to obtain cellulose. One of the possible appli‐ cations of cellulose is membrane synthesis, which has been reported for other bio‐ mass materials, such as sugarcane bagasse, mango seed and newspaper. In this chapter, some green pre-treatment methods, different sustainable routes for cellu‐ lose modification and some of the results obtained on membrane development based on waste biomass are discussed.

Characterization of a Microbial Consortium for the Bioremoval of Polycyclic Aromatic Hydrocarbons (PAHs) in Water

Pollution of freshwater ecosystems from polycyclic aromatic hydrocarbons (PAHs) is a global concern. The US Environmental Protection Agency (EPA) has included the PAHs pyrene, phenanthrene, and naphthalene among the 16 priority compounds of special concern for their toxicological effects. The aim of this study was to adapt and characterize a microbial consortium from ore waste with the potential to remove these three PAHs from water. This microbial consortium was exposed to the target PAHs at levels of 5, 10, 20, 50, and 100 mg L−1 for 14 days. PAH bioremoval was measured using the analytical technique of solid phase microextraction, followed by gas chromatography mass spectrometry (SPME-GC/MS). The results revealed that up to 90% of the target PAHs can be removed from water after 14 days at a concentration level of 100 mg L−1. The predominant group of microorganisms identified at the phylum taxonomic level were the Proteobacteria, while the Actinobacteria were the predominant subgroup. The removal of phenanthrene, naphthalene, and pyrene predominantly occurred in specimens of genera Stenotrophomonas, Williamsia, and Chitinophagaceae, respectively. This study demonstrates that the use of specific microorganisms is an alternative method of reducing PAH levels in water.