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Exposure to inorganic arsenic (iAs) remains a global public health problem. Urinary arsenicals are the current gold-standard for estimating both iAs exposure and iAs metabolism. However, the distribution of these arsenicals may differ between the urine and target organs. Instead, plasma arsenicals may better represent internal dose and capture target organ exposure to arsenicals. Drinking water iAs, plasma and urinary arsenicals were quantified in individuals living in the Zimapan and Lagunera regions of Mexico. The relationship between drinking water iAs and plasma arsenicals was examined using both Spearman correlations and multivariable linear regression models. In addition, the distribution of arsenicals in plasma and urine was examined and the association between plasma and urinary arsenicals was assessed using both Spearman correlations and multivariable linear regression models. Levels of iAs in drinking water were significantly associated with plasma arsenicals in unadjusted and adjusted analyses and the strength of these associations was similar to that of drinking water iAs and urinary arsenicals. These results suggest that plasma arsenicals are reliable biomarkers of iAs exposure via drinking water. However, there were notable differences between the profiles of arsenicals in the plasma and the urine. Key differences between the proportions of arsenicals in plasma and urine may indicate that urine and plasma arsenicals reflect different aspects of iAs toxicokinetics, including metabolism and excretion.

Mitochondrial dysfunction is a hallmark of diabetes, but the metabolic alterations during early stages of the disease remain unknown. The ability of liver cells to rearrange their metabolism plays an important role in compensating the energy shortage and may provide cell survival. Moringa oleifera leaves have been studied for its health properties against diabetes, insulin resistance, and non-alcoholic liver disease. We postulated that M. oleifera executes a protective function on mitochondrial functionality in HepG2 treated with high glucose. We evaluated the effect of high glucose treatment on the mitochondrial function of HepG2 cells using a Seahorse extracellular flux analyzer (Agilent, Santa Clara, CA, USA), blue native polyacrylamide gel electrophoresis (BN-PAGE), and western blot analysis. For assessment of mitochondrial abnormalities, we measured the activity of mitochondrial Complex I and IV as well as uncoupling protein 2, and sirtuin 3 protein contents. Our results demonstrate that, under conditions mimicking the hyperglycemia, Complex I activity, UCP2, Complex III and IV subunits content, supercomplex formation, and acetylation levels are modified with respect to the control condition. However, basal oxygen consumption rate was not affected and mitochondrial reactive oxygen species production remained unchanged in all groups. Treatment of HepG2 cells with M. oleifera extract significantly increased both protein content and mitochondrial complexes activities. Nonetheless, control cells’ respiratory control ratio (RCR) was 4.37 compared to high glucose treated cells’ RCR of 15.3, and glucose plus M. oleifera treated cells’ RCR of 5.2, this indicates high-quality mitochondria and efficient oxidative phosphorylation coupling. Additionally, the state app was not altered between different treatments, suggesting no alteration in respiratory fluxes. These findings enhance understanding of the actions of M. oleifera and suggest that the known antidiabetic property of this plant, at least in part, is mediated through modulating the mitochondrial respiratory chain.

High blood lead (BPb) levels in children and elevated soil and dust arsenic, cadmium, and lead were previously found in Torreón, northern Mexico, host to the world's fourth largest lead-zinc metal smelter. The objectives of this study were to determine spatial distributions of adolescents with higher BPb and creatinine-corrected urine total arsenic, cadmium, molybdenum, thallium, and uranium around the smelter. Cross-sectional study of 512 male and female subjects 12-15 years of age was conducted. We measured BPb by graphite furnace atomic absorption spectrometry and urine trace elements by inductively coupled plasma-mass spectrometry, with dynamic reaction cell mode for arsenic. We constructed multiple regression models including sociodemographic variables and adjusted for subject residence spatial correlation with spatial lag or error terms. We applied local indicators of spatial association statistics to model residuals to identify hot spots of significant spatial clusters of subjects with higher trace elements. We found spatial clusters of subjects with elevated BPb (range 3.6-14.7 μg/dl) and urine cadmium (0.18-1.14 μg/g creatinine) adjacent to and downwind of the smelter and elevated urine thallium (0.28-0.93 μg/g creatinine) and uranium (0.07-0.13 μg/g creatinine) near ore transport routes, former waste, and industrial discharge sites. The conclusion derived from this study was that spatial clustering of adolescents with high BPb and urine cadmium adjacent to and downwind of the smelter and residual waste pile, areas identified over a decade ago with high lead and cadmium in soil and dust, suggests that past and/or present plant operations continue to present health risks to children in those neighborhoods.

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.

We assessed the relationships between chronic arsenic (As) exposure, human papilloma virus (HPV) contact and non-melanoma skin cancer (NMSC) by means of a dermatology clinic-based case-control study (42 cases and 48 controls) in Region Lagunera, Mexico, where chronic As poisoning is endemic. Exposure was determined through detailed history of residence in the As-contaminated area and measurement of As levels in drinking water and urine. We used a consensus epitope from the central region of L1 protein of the HPV family to determine antibodies against HPV. A history of As exposure and HPV seropositivity were associated with increased NMSC risks. A history of exposure to high levels of As increased the risk for NMSC (OR = 4.53; P = 0.11) in the group of seronegative HPV patients. A positive response to HPV significantly increased the OR for NMSC to 9.04 (P = 0.01) when history showed exposure to low levels of As. Interestingly, the OR was significantly increased to 16.5 (P = 0.001) when both exposure to high levels of As and HPV seropositivity were present. In addition, the presence of NMSC increased the OR (5.45; P = 0.03) for a positive response to HPV when history showed exposure to low levels of As, but the OR was increased to 8.0 (P = 0.005) in the cases with high exposure levels. Thus, HPV infection could constitute an additional risk factor for NMSC development in humans chronically exposed to As. However, further studies with additional populations are needed to determine the interaction between HPV and As exposure in NMSC.

Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G > C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure.

The aim of this paper is to estimate the levels of arsenic (As) ingestion through cooked foods consumed in an arsenic endemic area and the assessment of their dietary intake of As. The study was conducted in two villages: a population chronically exposed to a high concentration of As via drinking water (410+/-35 microg/l) and to a low-exposure group (12+/-4 microg/l). A 24-h dietary recall questionnaire was applied to about 25 adult participants in each community. Samples of cooked food, ready for intake, were collected separately from each family's participants. To obtain the As estimate for each food item consumed, the mean quantity of food ingested in grams (wet weight) was calculated and the concentrations of total arsenic (TAs) in each cooked food were determined. The estimations of TAs intake were based on the sum over mean of As ingested from each food item consumed during the 24-h period for each participant. For the estimation of total daily As intake, we summed the mean obtained from food, plain water and hot beverage intakes. The TAs average intakes calculated for low-As-exposure group were 0.94 and 0.76 microg/kg body weight/day, for both summer and winter exposure scenarios, respectively. These values are 44.7 and 36% of the provisional tolerable daily intake (PTDI) for inorganic arsenic (2.14 microg/kg body weight/day), established by the World Health Organization (WHO) in 1989. The WHO reference value was obtained on a weekly basis intake estimation assuming an average body weight of 68 kg in adults. In contrast, for the high-exposure group the TAs average intakes were 16.6 and 12.3 microg/kg body weight/day for summer and winter, respectively. Ingestion via cooked food represented 32.5 and 43.9% of the total daily As intake in the high-exposure group; for summer and winter, respectively. None the less, the bioavailability of As through food can be different than via drinking water.

The selenium in the diet of persons in arsenic-endemic areas, high levels of arsenic in the drinking water, was evaluated. The methodology used was that of 24-hr dietary recall. Daily selenium intakes of two rural towns in northern Mexico were found to be similar, approximating 72.9 and 60.6 micrograms. These values were similar to those of a previously arsenic-exposed area from California, Edison community. The Edison participants had a daily selenium intake of 61.8 micrograms. The possible negative effect of selenium to produce differences in reported geographical variation in disease could not be substantiated in this study. Other nutrient intakes, protein and energy were also found similar for communities. Differences were noted in vitamin A intake where one-third the daily requirement was experienced by Mexican participants compared to two-thirds the requirement being satisfied by those participants from Edison.