Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where -0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

Alzheimer's Disease Association with Metals and Metalloids Concentration in Blood and Urine.

As there is some evidence that the risk for Alzheimer's disease (AD) is partially attributable to environmental exposure to some metals and metalloids, we examined an association between AD and arsenic, chromium, and selenium in 53 AD patients and 217 controls. Urinary arsenic, blood chromium, and selenium were determined by inductively coupled plasma mass spectrometry. Logistic regression models calculating odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate AD association with arsenic, chromium, and selenium. In AD patients, urinary arsenic and blood chromium were significantly higher, while blood selenium was significantly lower compared to controls. Increased blood selenium was related to a significant decrease in the odds of AD after adjustment for risk factors. Blood selenium per 1 kg × 10-9/m3 × 10-4 increment was associated with 1.4 times lower risk of AD (OR = 0.71; 95% CI 0.58-0.87). A significant increase in the odds of AD associated with increased blood chromium was also seen in the adjusted model: the OR per 1 kg × 10-9/m3 × 10-3 chromium increment was 2.39 (95% CI 1.32-4.31). The association of urinary arsenic with the risk of AD was not significant. The data obtained provide evidence that selenium reduces the risk of Alzheimer's disease, while chromium increases it.

Post-exposure distribution of selenium and aluminum ions and their effects on superoxide dismutase activity in mouse brain.

The study was conducted to determine how aluminum (Al) and selenium (Se) ions alone and in combination affect superoxide dismutase (SOD) activity and to evaluate the distribution of these elements in the blood and the brain of laboratory mice. SOD activity in mouse brain was evaluated after single-time (within 24 h) and repeated (over 14 days) intraperitoneal (IP) injections of SeO32-, Al3+, and (SeO32-+Al3+) solutions. The control mice received IP injections of the same volume of saline. Aluminum concentration in mouse blood increased both after single-time and repeated injections of AlCl3 and the combined (AlCl3 + Na2SeO3) solutions. The concentration of Se increased in blood after single-time and repeated injections of Na2SeO3 and the combined (AlCl3 + Na2SeO3) solutions. After the single-time injection of the experimental solutions, the concentrations of both Al and Se in mouse brain remained at baseline, but after repeated injections of (AlCl3 + Na2SeO3) solutions increased aluminum concentration. A single IP injection of Al did not change SOD activity in mouse brain, while a single injection of Se or the Se + Al mixture decreased it. After 14 days, IP injections of Al or Se alone did not affect SOD activity, while their combination decreased it. Our results showed that Se ions decreased SOD activity in mouse brain after both single-time and repeated IP injections of selenium-containing solutions. The study failed to show a direct or linear effect of increased Al or Se concentrations on SOD activity in mouse brain.