Selenium (Se) is an essential as well as a toxic trace element. Se intoxication has been reported in both livestock and humans. The central nervous system is sensitive to Se poisoning;exposure to Se causes blind stagg...
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Selenium (Se) is an essential as well as a toxic trace element. Se intoxication has been reported in both livestock and humans. The central nervous system is sensitive to Se poisoning;exposure to Se causes blind staggers in cattle, poliomyelomalacia in pigs, and nervous system disorders in humans. Differences in neurotoxicity between inorganic and organic Se have been demonstrated. In this study, groups of five male BALB/c mice each were administered sodium selenite or selenomethionine in drinking water ad libitum at 0, 1, 3, and 9 ppm as Se for 14 days. At the end of Se exposure, their brains were removed and dissected into different regions. The concentration of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindolacetic acid Q-HIAA) were determined in each brain region. Food and water consumption and body weight gain were significantly decreased in the group treated with the highest concentration of sodium selenite. In mice administered sodium selenite at 3 and 9 ppm, DOPAC was significantly higher in the striatum than in the control group. The striatal HVA was also increased in the group treated with 3 ppm Se;the DA showed a similar pattern, but the increase was not statistically significant. No alterations of NE, 5-HT, or 5-HIAA levels were detected in any brain region of mice treated with sodium selenite. No significant differences in any parameter among the groups treated with selenomethionine were observed indicating that inorganic Se was more neurotoxic than organic Se via drinking water. The alterations of DA metabolites by inorganic Se in DA-rich striatum suggested a Se-specific increased neural activity of dopaminergic pathways. Results may be useful in further elucidation of neurotoxicity of Se and in establishing a safe level of intake for this element.
Inorganic mercury (Hg2+) induced time- and concentration-dependent cellular injury in freshly isolated proximal tubular (PT) and distal tubular (DT) cells from normal (control) rats or uninephrectomized (NPX) rats. PT...
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Inorganic mercury (Hg2+) induced time- and concentration-dependent cellular injury in freshly isolated proximal tubular (PT) and distal tubular (DT) cells from normal (control) rats or uninephrectomized (NPX) rats. PT cells from NPX rats were more susceptible than PT cells from control rats, and DT cells were slightly more susceptible than PT cells to cellular injury induced by Hg2+ (not bound to a thiol). Preloading cells with glutathione increased Hg2+-induced cellular injury in PT cells from control rats. However, coincubation of PT or DT cells from control or NPX rats with Hg2+ and glutathione (1:4) provided significant protection relative to incubations with Hg2+ alone. No support was obtained for a role for gamma-glutamyltransferase in glutathione-dependent protection. However, the organic anion carrier does appear to play a role in accumulation and toxicity of mercuric conjugates of cysteine in PT cells from control, but not NPX, rats. Coincubation with Hg2+ and cysteine (1:4) had little effect on, or slightly enhanced, Hg2+-induced cellular injury at low concentrations of Hg2+ in all cells studied. Coincubation with Hg2+ and albumin (1:4) markedly protected PT and DT cells from control and NPX rats at all concentrations except the highest concentration of Hg2+ in DT cells from NPX rats. 2,3-Dimercapto-1-propanesulfonic acid protected cells both when preloaded or added simultaneously with Hg2+. Thus, renal cells from NPX rats are more susceptible to Hg2+-induced injury, PT and DT cells respond differently to exposure to Hg2+, and thiols can significantly modulate the toxic response to Hg2+.
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