Sodium selenite (Na 2 SeO 3 ) is the selenium form used in the composition of dietary supplements, and diphenyl diselenide (PhSe) 2 is an important intermediate in organic synthesis, which increases the risk of human exposure to this chemical in the workplace. These compounds have been reported to inhibit the cerebral and hepatic aminolevulinic acid dehydratase (ALA-D) in vitro, and now we show that ascorbic acid can reverse some alterations caused by in vivo selenium exposure, but not ALA-D inhibition. The effect of Na 2 SeO 3 or (PhSe) 2 and ascorbic acid on selenium distribution, total non-protein thiol, ascorbic acid content (liver and brain) and haemoglobin was also examined. Mice were exposed to 250 mmol/kg (PhSe) 2 , or 18.75 mmol/kg Na 2 SeO 3 subcutaneously, and to ascorbic acid, twice a day, 1 mmol/kg intraperitonially, for 10 days. Hepatic ALA-D of mice treated with (PhSe) 2 was inhibited about 58% and similar results were observed in the animals that received ascorbic acid supplementation (PϽ0.01, for (PhSe) 2 -treated and (PhSe) 2 πascorbic acid-treated mice). The haemoglobin content decreased after treatment with (PhSe) 2 (PϽ0.01). However, the haemoglobin content of the (PhSe) 2 πascorbic acid group was significantly higher than in the (PhSe) 2 -treated mice (PϽ0.05), and similar to control (PϾ0.10). Ascorbic acid treatment decreased significantly the hepatic and cerebral deposition of Se in (PhSe) 2 -exposed mice (PϽ0.01). Hepatic non-protein thiol content was not changed by treatment with (PhSe) 2 , ascorbic acid or (PhSe) 2 πascorbic acid. Hepatic content of ascorbic acid was twice that in mice that received (PhSe) 2 , independent of ascorbic acid treatment (PϽ0.001). The results of this study suggest that vitamin C may have a protective role in organodiselenide intoxication.

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The effects of acidic pH on the kinetics of Ca2+-ATPase isoforms from intracellular membranes of skeletal muscle, cardiac muscle, cerebellum and blood platelets were studied. At neutral pH, all four Ca2+-ATPase isoforms exhibited similar Ca2+-concentration requirements for half-maximal rates of Ca2+ uptake and ATP hydrolysis. A decrease in the pH from 7.0 to 6.0 promoted a decrease in both the apparent affinity for Ca2+ [increasing half-maximal activation (K0.5)] and the maximal velocity (Vmax) of Ca2+ uptake. With skeletal muscle vesicles these effect were 5 to 10 times smaller than those observed with all the other isoforms. Acidification of the medium from pH 7.0 to 6.5 caused the release of Ca2+ from loaded vesicles and a decrease in the amount of Ca2+ retained by the vesicles at the steady state. With the vesicles derived from skeletal muscle these effects were smaller than for vesicles derived from other tissues. The rate of passive Ca2+ efflux from skeletal and cardiac muscle vesicles, loaded with Ca2+ and diluted in a medium containing none of the ligands of Ca2+-ATPase, was the same at pH 7.0 and 6.0. In contrast, the rate of Ca2+ efflux from cerebellar and platelet vesicles increased 2-fold after acidification of the medium. The effects of DMSO, Mg2+ with Pi and arsenate on the rate of Ca2+ efflux varied among the different preparations tested. The differences became more pronounced when the pH of the medium was decreased from 7.0 to 6.0. It is proposed that the kinetic differences among the Ca2+-ATPase isoforms may reflect different adaptations to cellular acidosis, such as that which occurs during ischaemia.

Metallothionein (MT) proteins are widespread in bacteria, fungi, plants, and eukaryotic species. They are of low molecular weight (6-7 kDa) and of the 60+ amino acid residues, 20 are cysteines. Functions attributed to MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis; regulation of the biosynthesis and activity of zinc metalloproteins, most notably zinc-dependent transcription factors; and cellular cytoprotection from reactive oxygen species, ionizing radiation, electrophilic anticancer drugs and mutagens, and metals. Observations on the abundance of MTs within the central nervous system (CNS) and the identification of a brain-specific isoform, MT-III, suggest that it might have important neurophysiological and neuromodulatory functions. Reinforced by the potential involvement of MT-III in a number of neurodegenerative disorders, the role of MTs in the CNS has become an intense focus of scientific pursuit. This manuscript represents a survey on the ability of MTs to modulate mercury neurotoxicity, a neurotoxin that has been implied to play an etiologic role in Minamata disease, erethism, and autism, just to name a few.

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