Chronic exposure to inorganic arsenic and fluoride induces redox imbalance, inhibits the transsulfuration pathway, and alters glutamate receptor expression in the brain, resulting in memory impairment in adult male mouse offspring.

Exposure to toxic elements in drinking water, such as arsenic (As) and fluoride (F), starts at gestation and has been associated with memory and learning deficits in children. Studies in which rodents underwent mechanistic single exposure to As or F showed that the neurotoxic effects are associated with their capacity to disrupt redox balance, mainly by diminishing glutathione (GSH) levels, altering glutamate disposal, and altering glutamate receptor expression, which disrupts synaptic transmission. Elevated levels of As and F are common in groundwater worldwide.

Decreased Arsenic Disposition and Alteration of its Metabolic Profile in mice Coexposed to Fluoride.

Inorganic arsenic (iAs) and fluoride (iF) are ubiquitous elements whose coexistence is frequent in several regions of the world due to the natural contamination of water sources destined for human consumption. It has been reported that coexposure to these two elements in water can cause toxic effects on health, which are controversial since antagonistic and synergistic effects have been reported. However, there is little information on the possible toxicological interaction between concurrent exposure to iAs and iF on the iAs metabolism profile.

Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

Background: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic.

Objective: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water.

Methods: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico.

Fluoride exposure is associated with altered metabolism of arsenic in an adult Mexican population.

Arsenic (As) and fluoride (F) are two common groundwater toxicants. The toxicity of As is closely related to As metabolism, and several biological and environmental factors have been associated with As modification. However, limited information about the effect of F exposure on the modification of the As metabolism profile has been described.

The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs.

Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic.

Background: Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure-related cardiovascular disease in children.

Urinary arsenic levels influenced by abandoned mine tailings in the Southernmost Baja California Peninsula, Mexico.

Gold has been mined at San Antonio-El Triunfo, (Baja California Sur, Mexico) since the 18th century. This area has approximately 5,700 inhabitants living in the San Juan de Los Planes and El Carrizal hydrographic basins, close to more than 100 abandoned mining sites containing tailings contaminated with potentially toxic elements such as arsenic. To evaluate the arsenic exposure of humans living in the surrounding areas, urinary arsenic species, such as inorganic arsenic (iAs) and the metabolites mono-methylated (MMA) and di-methylated arsenic acids (DMA), were evaluated in 275 residents (18-84 years of age).

Environmental exposure to arsenic, AS3MT polymorphism and prevalence of diabetes in Mexico.

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes. We previously reported an association of diabetes and urinary concentration of dimethylarsinite (DMAs(III)), a toxic product of arsenic methylation by arsenic (+3 oxidation state) methyltransferase (AS3MT). Here we examine associations between AS3MT polymorphism, arsenic metabolism and diabetes.

Dose-dependent urinary phenotype of inorganic arsenic methylation in mice with a focus on trivalent methylated metabolites.

Inorganic arsenic (iAs) exposure has been associated with the increased risk of various forms of cancer and of non-cancerous 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. However, in vivo research involving the production of MAsIII and DMAsIII remains an area of ongoing investigation and debate.

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico.

Background: Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico.

Arsenic species, AS3MT amount, and AS3MT gene expression in different brain regions of mouse exposed to arsenite.

Human exposure to inorganic arsenic (iAs) has been associated with cancer and serious injury to various internal organs, as well as peripheral neuropathy, endocrine disruption and diverse effects in the central nervous system (CNS). Using rodent models, it is possible to demonstrate As accumulation in the brain that leads to defects in operant learning, behavioral changes, and affect pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process, yielding products that are more reactive and toxic than the parent compound.

Arsenite induces aquaglyceroporin 9 expression in murine livers.

Mice exposed to sodium arsenite show a dose-related accumulation of inorganic arsenic (iAs) and its methylated metabolites in the liver. While the accumulation of iAs forms increased linearly with dose in liver cells, a different pattern was observed in other tissues such as the brain and lung, as well as in the peripheral nerves of the rat. As such, trivalent iAs enters the cells, using aquaglyceroporin transporters to modulate cell arsenic accumulation and cytotoxicity.

Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesions.

Exposure to naturally occurring inorganic arsenic (iAs), primarily from contaminated drinking water, is considered one of the top environmental health threats worldwide. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the biotransformation pathway of iAs. AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenicals, resulting in the production of methylated (MAs) and dimethylated arsenicals (DMAs).

Estrogens and human papilloma virus oncogenes regulate human ether-à-go-go-1 potassium channel expression.

Ether-à-go-go-1 (Eag1) potassium channels are potential tools for detection and therapy of numerous cancers. Here, we show human Eag1 (hEag1) regulation by cancer-associated factors. We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7).

Inorganic arsenic exposure affects pain behavior and inflammatory response in rat.

Inorganic arsenic (iAs) contamination of drinking water is a worldwide problem associated with an increased risk for the development of various types of cancer and noncancerous damage. In vitro studies have suggested that iAs can modulate the activity of macrophages producing an over-expression of cyclooxygenase-2 (COX-2) and resulting in an increase in prostaglandin E(2) (PGE(2)) concentrations in endothelial cells. These effects may lead to an in vivo enhancement of inflammatory and pain responses.

Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite.

Recent epidemiologic studies have associated chronic inorganic arsenic ((i)As) exposure with an increase in the prevalence of diabetes mellitus. Currently, the diabetogenic mechanism caused by (i)As exposure is unclear. However, it is recognized that (i)As contributes to oxidative stress in several organs and systems through generation of reactive oxygen species (ROS).