Bioaccessibility of arsenic from contaminated soils and alteration of the gut microbiome in an in vitro gastrointestinal model.

Arsenic exposure has been reported to alter the gut microbiome in mice. Activity of the gut microbiome derived from fecal microbiota has been found to affect arsenic bioaccessibility in an in vitro gastrointestinal (GI) model. Only a few studies have explored the relation between arsenic exposure and changes in the composition of the gut microbiome and in arsenic bioaccessibility.

Bioavailable soil Pb minimized by in situ transformation to plumbojarosite.

Exposure to lead (Pb) during early life has persistent adverse health effects. During childhood, ingestion of bioavailable Pb in contaminated soils can be a major route of Pb absorption. Remediation to alter physiochemical properties of soil-borne Pb can reduce Pb bioavailability.

Intra- and Interlaboratory Evaluation of an Assay of Soil Arsenic Relative Bioavailability in Mice.

Hand-to-mouth activity in children can be an important route for ingestion of soil and dust contaminated with inorganic arsenic. Estimating the relative bioavailability of arsenic present in these media is a critical element in assessing the risks associated with aggregate exposure to this toxic metalloid during their early life. Here, we evaluated the performance of a mouse assay for arsenic bioavailability in two laboratories using a suite of 10 soils.

Dietary Lead and Phosphate Interactions Affect Oral Bioavailability of Soil Lead in the Mouse.

Effects of dietary P level on the oral bioavailability of Pb present in soil were examined in a mouse model. Adult female C57BL/6 mice had free access to AIN-93G purified rodent diet amended with Pb as a soluble salt, Pb acetate, or in a soil matrix (NIST SRM 2710a). In these studies, the basal diet contained P at a nutritionally sufficient level (0.

An in vitro assessment of bioaccessibility of arsenicals in rice and the use of this estimate within a probabilistic exposure model.

In this study, an in vitro synthetic gastrointestinal extraction protocol was used to estimate bioaccessibility of different arsenicals present in 17 rice samples of various grain types that were collected across the United States. The across matrix average for total arsenic was 209 ng/g±153 (\[xmacr]±2σ). The bioaccessibility estimate produced an across matrix average of 61%±19 (\[xmacr]±2σ).

Preabsorptive metabolism of sodium arsenate by anaerobic microbiota of mouse cecum forms a variety of methylated and thiolated arsenicals.

The conventional scheme for arsenic methylation accounts for methylated oxyarsenical production but not for thioarsenical formation. Here, we report that in vitro anaerobic microbiota of mouse cecum converts arsenate into oxy- and thio- arsenicals. Besides methylarsonic acid (MMA(V)), arsenate was transformed into six unique metabolites: mono-, di-, and trithio-arsenic acid, monomethyldithio- and monomethyltrithio-arsonic acid, and dimethyldithioarsonic acid.

Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice.

The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, female As3mt knockout (KO) mice treated with diet containing 100 or 150 ppm arsenic as arsenite showed systemic toxicity and significant effects on the urothelium. In the present study, we showed that the cytotoxic and proliferative effects of arsenite administration on the urothelium are dose dependent.

Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice.

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5mg of arsenic as arsenate per kilogram of body weight.

Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+3 oxidation state) methyltransferase knockout mice. A preliminary report.

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n=8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As(III)).

Disruption of the arsenic (+3 oxidation state) methyltransferase gene in the mouse alters the phenotype for methylation of arsenic and affects distribution and retention of orally administered arsenate.

The arsenic (+3 oxidation state) methyltransferase (As3mt) gene encodes a 43 kDa protein that catalyzes methylation of inorganic arsenic. Altered expression of AS3MT in cultured human cells controls arsenic methylation phenotypes, suggesting a critical role in arsenic metabolism. Because methylated arsenicals mediate some toxic or carcinogenic effects linked to inorganic arsenic exposure, studies of the fate and effects of arsenicals in mice which cannot methylate arsenic could be instructive.

Exploring the in vitro formation of trimethylarsine sulfide from dimethylthioarsinic acid in anaerobic microflora of mouse cecum using HPLC-ICP-MS and HPLC-ESI-MS.

Although metabolism of arsenicals to form methylated oxoarsenical species has been extensively studied, less is known about the formation of thiolated arsenical species that have recently been detected as urinary metabolites. Indeed, their presence suggests that the metabolism of ingested arsenic is more complex than previously thought. Recent reports have shown that thiolated arsenicals can be produced by the anaerobic microflora of the mouse cecum, suggesting that metabolism prior to systemic absorption may be a significant determinant of the pattern and extent of exposure to various arsenic-containing species.

In vitro biotransformation of an arsenosugar by mouse anaerobic cecal microflora and cecal tissue as examined using IC-ICP-MS and LC-ESI-MS/MS.

This investigation examined chemical and microbiological transformations of an arsenosugar by mouse cecum. To mimic the low oxygen environment in the mammalian gastrointestinal tract, reaction mixtures were incubated under anaerobic conditions. An arsenosugar extracted from ribbon kelp, 3-[5'-deoxy-5-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropanesulfonic acid, As392, was added to reaction mixtures that contained either cecal microflora or cecal tissue homogenate.

A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol.

S-Adenosyl-l-methionine (AdoMet):arsenic(III) methyltransferase, purified from liver cytosol of adult male Fischer 344 rats, catalyzes transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. The kinetics of production of methylated arsenicals in reaction mixtures containing enzyme, AdoMet, dithiothreitol, glutathione (GSH), and arsenite are consistent with a scheme in which monomethylated arsenical produced from arsenite is the substrate for a second methylation reaction that yields dimethylated arsenical. The mRNA for this protein predicts a 369-amino acid residue protein (molecular mass 41056) that contains common methyltransferase sequence motifs.