Inorganic
arsenic exposure via
drinking water has been associated with
cancer and serious injury in various internal organs, as well as with
peripheral neuropathy and diverse effects in the nervous system. Alterations in memory and attention processes have been reported in exposed children, whereas adults acutely exposed to high amounts of inorganic
arsenic showed impairments in learning, memory, and concentration.
Glutathione (GSH) is extensively involved in the metabolism of inorganic
arsenic, and both
arsenite and its methylated metabolites have been shown to be potent inhibitors of
glutathione reductase (GR) in vitro. Brain would be more susceptible to GR inhibition because of the decreased activities of
superoxide dismutase (SOD) and
catalase reported in this tissue. To investigate whether GR inhibition could be documented in vivo, we determined the activity and levels of GR in brain as well as in liver, the main organ of
arsenic metabolism in mice exposed to 2.5, 5, or 10 mg/kg/day of
sodium arsenite over a period of 9 days. In contrast to what has been observed in vitro, significant inhibition of the expression and activity of GR was observed only at the highest concentration used (10 mg/kg/day) in both organs. Although the disposition of
arsenicals was higher in liver, significant amounts of inorganic and methylated
arsenic forms were determined in the brain of exposed animals. The formation of monomethylarsenic (MMA) and dimethylarsenic (DMA) metabolites in the brain was confirmed by incubating brain slices for 24, 48, and 72 h with
sodium arsenite.