Trivalent arsenic species induce changes in expression and levels of proinflammatory cytokines in intestinal epithelial cells.

Chronic arsenic (As) toxicity in humans has been documented in many countries where exposure mostly occurs through drinking water. The As immunotoxic effects have been demonstrated in animal models as well as in humans. The studies of the immunotoxicity of As have centered on organs related to immune response or target organs, with few data being available at intestinal level. The present study has evaluated the changes in the expression and release of cytokines in Caco-2 cells, widely used as an intestinal epithelial model. Differentiated cells were exposed to 1 µM of As(III), 0.1 µM of monomethylarsonous acid [MMA(III)] and 1 µM of dimethylarsinous acid [DMA(III)] during 2, 4, 6 and 24 h. Additionally, the effect of As coexposure with lipopolysaccharide (LPS, 10 ng/mL) has been evaluated. The results show trivalent species to induce increases in the expression and release of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), IL6, IL8 - the magnitude and time of response being different for each As species. The response of greatest magnitude corresponds to DMA(III), followed by As(III), while MMA(III) generates a limited response. Furthermore, the presence of LPS in the co-exposed cells could affect the expression and secretion of cytokines compared with individual exposure to arsenicals, especially for As(III)/LPS and DMA(III)/LPS.

Arsenic and fluoride induce neural progenitor cell apoptosis.

The aim of the present study is to determine the effect of inorganic arsenic (As) and its metabolites on the viability of the neural progenitor cell (NPC) line C17.2, in order to evaluate cellular mechanisms involved in As developmental neurotoxicity. Moreover, we analyzed the effects of the coexposure to As and fluoride (F), a situation to which some populations are commonly exposed. Our results show that NPCs are not susceptible to pentavalent As species [arsenate, monomethylarsonic acid, and dimethylarsinic acid] and F alone. However, the trivalent metabolites of arsenate [arsenite, monomethylarsonous acid, and dimethylarsinous acid] are toxic at concentrations below 1 mg/l, and this susceptibility increases when there is coexposure with F (≥ 5 mg/l). Arsenite triggers apoptosis after 24 h of exposure, whereas monomethylarsonous acid produces necrosis at very short times (2 h). Arsenite leads to an increase in intracellular Ca levels and generation of reactive oxygen species, which may cause a decrease in mitochondrial transmembrane potential, release of cytochrome c, and consequent activation of caspases. A slight activation of calpain also takes place, which might favor activation of the mitochondrial pathway or might activate other pathways. The treatment with some antioxidants such as quercetin and α-tocopherol shows only a partial reduction of the cytotoxicity.

Wine yeast strains engineered for glycogen overproduction display enhanced viability under glucose deprivation conditions.

We used metabolic engineering to produce wine yeasts with enhanced resistance to glucose deprivation conditions. Glycogen metabolism was genetically modified to overproduce glycogen by increasing the glycogen synthase activity and eliminating glycogen phosphorylase activity. All of the modified strains had a higher glycogen content at the stationary phase, but accumulation was still regulated during growth. Strains lacking GPH1, which encodes glycogen phosphorylase, are unable to mobilize glycogen. Enhanced viability under glucose deprivation conditions occurs when glycogen accumulates in the strain that overexpresses GSY2, which encodes glycogen synthase and maintains normal glycogen phosphorylase activity. This enhanced viability is observed under laboratory growth conditions and under vinification conditions in synthetic and natural musts. Wines obtained from this modified strain and from the parental wild-type strain don't differ significantly in the analyzed enological parameters. The engineered strain might better resist some stages of nutrient depletion during industrial use.