Both inorganic and organic selenium supplements can decrease brain monoamine oxidase b enzyme activity in adult rats

British Journal of Nutrition (2008), page 1 of 6 Both inorganic and organic selenium supplements can decrease brainmonoamine oxidase B enzyme activity in adult rats Ya-Li Tang1, Shih-Wei Wang2 and Shyh-Mirn Lin1*1Department of Food and Nutrition, Chung Hwa University of Medical Technology, no. 89, Wenhwa 1st Street, Tainan County 717,Taiwan2Graduate Institute of Biological Science and Technology, Chung Hwa University of Medical Technology, no. 89, Wenhwa 1stStreet, Tainan County 717, Taiwan (Received 19 June 2007 – Revised 14 December 2007 – Accepted 17 December 2007) It has been observed that the levels of brain monoamine oxidase B (MAO-B) increase during ageing. MAO catalyses the oxidative deamination ofneurotransmitters, in which the by-product H2O2 is subsequently generated. Se exists naturally in inorganic and organic forms and is considered toplay a key role in antioxidation functioning. The objective of the present study was to investigate two chemical forms of Se compounds for theirinhibition effect on rat brain MAO-B. The total antioxidant capacity and lipid peroxidation of rats were also examined. The rats (age 7 weeks) weredivided into four groups: the control group, tocopherol group (T group, positive control), selenite group (SE group, representing the inorganicSe group) and seleno-yeast group (SY group, representing the organic Se group). The rats were fed for 11 weeks with normal diets and 12weeks with test diets. The serum total antioxidant capacity of the SE and SY groups was significantly higher than that in the control and T groups. In rat brains and livers, the lipid peroxidation levels were significantly decreased in the T, SE and SY groups. MAO-B activityshowed a significant decrease in the T, SE and SY groups in rat brains but no significant change could be noted in the rat livers. In conclusion, the present study indicates that inorganic or organic Se supplementation can decrease the brain MAO-B enzyme activity in adult rats and can beaccomplished by the effect of the Se antioxidation capability.
Selenium: Seleno-yeast: Monoamine oxidase B: Brain: Antioxidation Monoamine oxidase (MAO; E.C. 1.4.3.4) is an enzyme that possesses many benefits including protection against oxidative has two isoenzymes: type A and B. It is widely distributed damage, reduction of cancer risk and regulation of immune func- in tissues including the nerves, kidneys, liver and gastrointes- tion(9 – 11). Se exists naturally in inorganic (for example, selenite tinal tract. The enzyme catalyses the metabolism of biologi- and selenate) and organic (for example, seleno-yeast, seleno- cally active amine compounds and participates in the methionine and selenocysteine) forms. These two forms vary oxidative deamination reaction of a variety of amine neuro- in bioavailability and protective effects(12 – 14). As determined transmitters, such as dopamine, adrenaline, serotonin, etc(1).
by the glutathione peroxidase activity and Se concentrations in Because of the observation that MAO-B levels are increased tissue, organic Se sources are absorbed and retained more effi- during ageing(2,3), the relationship between MAO-B and ciently than the inorganic Se sources(15,16). In mammals, dra- ageing-related diseases has been extensively discussed.
matic differences are found in the uptake and binding of Several neurodegenerative diseases, such as Parkinson’s and selenite and selenomethionine by brush-border membrane ves- Alzheimer’s, reveal high MAO-B in the brain, but have no icles(17). For the purpose of Se supplementation, selenite, seleno- difference in MAO-A(1,2,4,5). In addition, inhibitors of MAO- methionine and seleno-yeast are usually administered as B have been applied to Alzheimer’s patients, in whom commercial products in diets. Yeast (Saccharomyces cerevi- improvements have been observed(6 – 8).
siae) can uptake Se and most of the total Se is converted to the Se is a dietary essential trace element for humans. Se can be form of selenomethionine(14). For this reason, selenomethionine incorporated into selenoproteins in the form of selenocysteine is the major Se compound in seleno-yeast.
and selenomethionine. It is also necessary for Se-containing The relationship between Se and brain function is also enzymes, such as glutathione peroxidase. Glutathione peroxi- another interesting topic. It becomes more and more apparent dase can take part in the catalysing of H2O2 to water and, conse- that Se plays a critical role in the maintenance and modulation quently, it contributes to antioxidation. Therefore, Se plays a key of brain functions(18). Se is involved in the conservation of role in antioxidation functioning. It is well known that Se functional brain activity and protects against the oxidative Abbreviations: MAO, monoamine oxidase; ppm, parts per million; SE group, selenite group; SY group, seleno-yeast group; T group, tocopherol group; TBARS, thiobarbituric acid-reactive substances.
* Corresponding author: Dr Shyh-Mirn Lin, fax þ 886 6 2605779, email lsm@mail.hwai.edu.tw stress-related brain disorders, such as Parkinson’s disease and brain damage(19,20). It is widely accepted that oxidative stressis involved in the degeneration of dopaminergic cells, possibly or by the auto-oxidation of dopamine(21,22). H2O2 can be eliminated by glutathione peroxidase, an Se-containing enzyme. Se chemical compounds have also been suggested for use in Alzheimer’s disease prevention trials(23).
It has been observed that there was an increase of dopamine turnover in rats that were fed on an Se-deficient diet(24). How- ever, there are few publications that have proposed the relationship between MAO-B enzyme activity and supple- menting with different types of Se compounds in adult rats.
In summary for the correlation among Se, MAO-B, ageing and other oxidative brain damage we would like to propose the possibility of Se influence on the MAO-B reaction.
Because of the different chemical forms and distinct bioavail- ability, we selected two chemical forms of Se compounds for their inhibition effect on MAO-B. The present study was undertaken in order to discuss the possibility of the preventioncapability of Se on MAO-B enzyme activity in adult rats.
were removed and stored at 2 808C for the experiments asdescribed below.
Serum oxygen-radical absorbance capacity assay AIN-76-based diets were purchased from ICN Biomedicals The total antioxidant capacity in the serum of rats was (Los Angeles, CA, USA). The a-tocopherol, sodium selenite, estimated by an oxygen-radical absorbance capacity assay(25).
2,2-azobis (2-amidinopropane) dihydrochloride, b-phycoery- The 0·01 ml diluted rat serum contained 2,2-azobis (2-amidino- thrin, Trolox, TCA, thiobarbituric acid, 2,6-ditertbutyl-4- propane) dihydrochloride (75 mM; 0·01 ml), b-phycoerythrin methylphenol and benzylamine were all purchased from (0·4 mM; 0·015 ml) and sodium phosphate buffer to 0·25 ml Sigma Chemical Co. (St Louis, MO, USA). Seleno-yeast final volume. The assay mixture was incubated at 378C was supplied by the product VIVA Selenium Yeast (Westar and the fluorescence was measured at an excitation wavelength Nutrition Corp., Costa Mesa, CA, USA).
of 492 nm and an emission wavelength of 565 nm for 200 min.
Trolox was used for the standard curve and antioxidant equiv-alent calculations. The final results were calculated using the differences of the areas under the fluorescence curves during The experimental design was approved by the Animal Exper- 200 min, in which they were expressed as mmol Trolox equiva- iment Committee of Chung Hwa University of Medical Tech- nology. Twenty-four male Long – Evans rats (age 7 weeks)were purchased from the National Laboratory Animal Center.
Rats were housed individually in stainless-steel wire-bottomedcages in a room with a controlled temperature and 12 h light Lipid peroxidation in rat brains and livers was estimated fluor- and dark cycles. Food and distilled water were provided ad libi- escently by the modified thiobarbituric acid-reactive substances tum. The animals were fed on chow diets for 10 weeks and (TBARS) method(26). In brief, 0·5 ml of tissue homogenate (in then were fed on diets based on AIN-76 for 1 week. Then, the potassium phosphate buffer, pH 7·4) was treated with 0·5 ml of rats were divided into four groups: control group, tocopherol TCA solution (10 %) and centrifuged at 1500 g for 10 min. The group (T group, positive control), selenite group (SE group, clear supernatant fraction was collected and treated with thio- representing the inorganic sodium selenite supplement group) barbituric acid solution (0·4 % in 0·2 M-HCl) and 2,6-ditertbu- and seleno-yeast group (SY group, representing the organic tyl-4-methylphenol (0·2 % in 95 % ethanol), and then placed in seleno-yeast supplement group). The assigned procedure was a 508C water-bath for 1 h. n-Butanol was added to the cooled randomly by body weight in order to equalise the mean solution and centrifuged at 1500 g for 10 min. The clear super- body weight of the rats in each group. The compositions of the natant fraction was collected and used for the measurement experimental diets for the four groups are shown in of fluorescence at an excitation wavelength of 515 nm and The concentration of Se in the fortified test diets was adjusted an emission wavelength of 550 nm (Hitachi F-4500 Fluor- to 2 mg Se equivalent per kg diet in the SE and SY groups.
escence Spectrophotometer; Hitachi, Tokyo, Japan).
Food intake and body weight were recorded every 3 d.
After 12 weeks, adult rats were fasted for 12 h and then were killed by carbon dioxide inhalation. Their blood wascollected into tubes followed by centrifugation (3000 g; MAO-B enzyme activity in rat tissue was measured by a 20 min; 48C) to separate the serum. The rat brains and livers modification of a standard assay procedure(27). Tissues were Brain monoamine oxidase decreased by selenium homogenised in 0·2 M-phosphate buffer (pH 7·4) and centri- The lipid peroxidation status in the brains and livers of the fuged at 1000 g for 10 min (48C). The supernatant fraction control, T, SE and SY groups of rats was tested by the was collected and further centrifuged at 17 000 g for 30 min TBARS method. The brain and liver relative TBARS levels of (48C). The pellet was collected and re-suspended in 1 ml phos- the rats that were fed on four test diets for 12 weeks are shown phate buffer (0·2 M; pH 7·4). Benzylamine solution (0·3 ml; in In the rat brains, the TBARS levels were significantly 8 mM) was added to 0·125 ml re-suspended pellet solution, decreased in the T, SE and SY groups (P, 0·05) (a)). A and then adjusted to the final volume of 3 ml by phosphate significant decrease in the rat liver TBARS levels of the T, SE buffer. The mixture was shaken at 378C for 3 h. The reaction and SY groups were also shown (P, 0·05) (b)). It was was stopped by the addition of 0·3 ml of 60 % perchloric acid.
demonstrated that the inorganic Se (selenite) and organic The reaction product benzylaldehyde was extracted with 3 ml Se (seleno-yeast) supplements exhibit a similar lipid peroxi- cyclohexane. The organic phase was separated by centrifu- dation-preventive effect on a-tocopherol in rats, which is gation at 3000 g for 10 min, and read for absorbance at 242 nm (Hitachi U-2001 spectrophotometer). The protein The MAO-B enzyme activities in rat brains and livers are concentration assay method was used as described by shown in In the rat brains, MAO-B activity showed a Lowry et al. (28). For verifying purposes, pargyline (MAO-B significant decrease in the T, SE and SY groups (P, 0·05).
inhibitor) was used to confirm the type of MAO isoforms.
However, no significant change could be noted with respectto MAO-B activities in the rat livers between each group.
For confirming the type of MAO isoforms, we also tested the MAO type by treating pargyline (MAO-B inhibitor) in par- Values are presented as means and standard deviations from tial tissue samples and demonstrated a decrease in MAO-B all the sets of independent experiments. Differences between the groups were studied by using one-way ANOVA, followed The correlation statistical analyses among the total antioxi- by Duncan’s multiple-range test. Differences between the con- dant capacity, lipid peroxidation and MAO activity are shown trol and experimental groups for all the parameters were ana- in Brain MAO activity has a positive correlation with lysed by using Student’s t test. The difference was considered brain and liver lipid peroxidation. Nevertheless, liver MAO has significant when P was 0·05 or less. The correlation among the a negative correlation with serum total antioxidant capacity.
serum oxygen-radical absorbance capacity, brain TBARS, In addition, there is a negative correlation between serum liver TBARS, brain MAO and liver MAO was analysed by total antioxidant capacity and brain lipid peroxidation, and a using the Pearson correlation. Statistical analysis was furth- positive correlation between brain and liver lipid peroxidation.
ered by using a SAS statistical computer program (version13.0.161; SAS Institute Inc., Cary, NC, USA).
Se is an essential micronutrient at levels of about 0·1 parts per million (ppm) in the animal diet, but it is toxic at levels of 8 or The data for the rats that were fed on test diets through the 10 ppm(12,29). Moreover, Se possesses advanced effects, such experimental period are shown in At the end of 12 as anticarcinogenesis, usually at levels above dietary require- weeks of Se supplementation, there were no significant differ- ment in the range of 1 – 5 ppm(12). In this experiment, control ences in the rats’ body weight, body-weight gain, food intake and T group diets provided 0·1 mg Se/kg. It is the standard diet or feed efficiency between the four groups. This shows that the recommended by the American Institute of Nutrition for fortified constituents have no influence on rat growth and food growth and maintenance of rodents. Similarly, previous intake. However, after the rats were fed on test diets for 12 studies indicated that 0·1 mg Se/kg diet provides an Se-ade- weeks, the SE and SY groups’ serum total antioxidant quate intake for rats(30). The Se doses used in the SE and capacity was significantly higher than that in the control and SY groups were high for rats. To realise the advanced effect T groups (P, 0·05) In addition, the T group had no of Se supplementation, the Se administration level in the SE marked differences from the control group. The SE and and SY groups should be increased more than adequate dietary SY groups were shown to have an equal effect of the total content. Se (as sodium selenite) dietary formulas of 0·2 antioxidant capacity compared with the other groups.
and 2 mg/kg have been used to ascertain chemopreventive Table 2. Body-weight gain, food intake and feed efficiency of the rats fed on test diets (eight rats per group)* * There are no significant differences between the groups (Duncan’s multiple-range test; P, 0·05).
Fig. 1. The effect of total antioxidant capacity in the serum of rats fed control (c), tocopherol supplement (T), sodium selenite supplement (SE) and seleno-yeast supplement (SY) diets for 12 weeks. Values are means for seven or eight rats, with standard deviations represented by vertical bars. * Mean value is significantly different from that of the control group (P, 0·05; Student’s t test). ORAC, oxygen-radical absorbance capacity.
mechanisms of Se in rats and mice(31). It has previously also been demonstrated that when fed in a diet supplementedwith 3 ppm Se (as either sodium selenite and Se-garlic), Se exerts its cancer-preventive activity(32). In addition, diets con-taining either 0·225 or 4·2 mg Se/kg (as sodium selenite) were Fig. 3. Brain (a) and liver (b) monoamine oxidase (MAO) activity of rats fed fed as part of the design in rat heart function research(33). Con- control (c), tocopherol supplement (T), sodium selenite supplement (SE) and sidering these dietary supplementations, 2 mg Se/kg may be seleno-yeast supplement (SY) diets for 12 weeks. Activity is given in units(U) of nmol/h per mg protein. Values are means for seven or eight rats, with appropriate to apply in the SE and SY groups.
standard deviations represented by vertical bars. * Mean value is significantly There have been mounting discussions about MAO-B, different from that of the control group (P, 0·05; Student’s t test).
focusing on neurotransmitter regulations, ageing-concerneddiseases, molecular mechanisms, enzyme inhibitors, and so We found that selenite or seleno-yeast supplements can on. However, only a few reports have been discussed regard- increase the total antioxidant capacity in the serum of rats ing the relationship between supplementation and MAO-B In contrast to this finding, in earlier work about enzyme regulation. In the present study, we investigated the long-term Se deficiency rat arterial walls, a significant antioxidation regulation and MAO-B activity moderation decrease was observed in the total antioxidant capacity, and effect of inorganic and organic Se supplements in adult rats.
an increase was observed after 1 month of Se (sodium sele-nite) supplementation(34). In addition, moderate Se supplemen-tation (as sodium selenite or as Se-rich food) caused an increase in the total antioxidant activity in rat hearts(35).
Nevertheless, there are fewer studies noted about seleno- yeast supplementation for the effect of total antioxidant capacity. The T (a-tocopherol supplement) group showed no significant difference from the control group (see The total antioxidant capacity assay of rat serum in ourresearch was evaluated according to the oxygen-radical absor-bance capacity method which is based on the absorbance capacity of oxygen radicals by antioxidants. However, the Table 3. Correlation among total antioxidant capacity, lipid peroxidation Fig. 2. The brain (a) and liver (b) relative thiobarbituric acid reactive sub- stances (TBARS) fluorescence of rats fed control(c), tocopherol supplement (T), sodium selenite supplement (SE) and seleno-yeast supplement (SY) diets for 12 weeks. Values are means for seven or eight rats, with standarddeviations represented by vertical bars. * Mean value is significantly different TBARS, thiobarbituric acid reactive substances; ORAC, oxygen-radical absorbance from that of the control group (P, 0·05; Student’s t test).
Brain monoamine oxidase decreased by selenium reaction of a-tocopherol is not a reaction with oxygen, but activity. We propose that lipid peroxidation should play an with fatty acid peroxyl radicals, and intercepts the chain reac- important role in brain MAO activity. There are reverse tion. Thus the antioxidant reaction is not the removal of results of these correlations among liver MAO activity, oxygen but the interception of the auto-oxidation radical serum total antioxidant capacity, and brain and liver lipid per- chain process which is perpetuated by fatty acids(36). It may oxidation. The results can at least partly explain the diverse be due to this that T groups showed no significant difference inhibition effect of Se supplements on brain and liver MAO from the control group. Because of the reaction features, toco- pherol would protect lipid peroxidation and cause a decrease It is well known that MAO inhibitors, such as pargyline and in the TBARS assay level. It also explains the result that a sig- L-deprenyl, have been shown to protect against central nervous nificant decrease was observed in the T group of the rat system oxygen toxicity in rats by decreasing intracellular H2Oþ production from the oxidation of catecholamine in the Previous studies proposed that selegiline, a selective irre- brain(43,44). In addition, MAO inhibitors possess the thera- versible MAO-B inhibitor, is able to reduce the TBARS peutic value of MAO inhibition effect in the treatment of Par- levels in rat brain tissue(37,38). In the present study, it was kinson’s disease and depressive illness, although some side demonstrated that there is a positive correlation between effects are still unavoidable(44,45). Some MAO inhibitors brain MAO activity and lipid peroxidation of brain and liver showed further advances of tissue selectivity in that they inhib- A possible link between MAO activity and lipid ited MAO enzymes in the brain, but caused little inhibition of peroxidation can be assumed, at least in part, which remains the enzymes in the liver(46,47). Nevertheless, supplementation for further investigation. However, since the similar protective may be the better pathway for neuroprotection, which can be action to lipid peroxidation of the T, SE and SY groups was applied daily. In the present study, we suggest that inorganic shown in both rat brains and livers this shows that or organic Se supplementation can decrease brain MAO-B these antioxidants may affect the rat physiological function enzyme activity in adult rats. Furthermore, our research pro- and in turn lead to a lipid peroxidative protection effect.
poses the possible application of Se supplements for the These results can be explained by the important role of Se tissue-selective effect of dietary MAO-B inhibitors.
in preventing lipid peroxidation(39 – 41).
MAO-B levels are increased during ageing(2,3). Neverthe- less, the T, SE and SY groups demonstrated a significant decrease in MAO-B activity compared with the control group in rat brains. Brain MAO catalyses the oxidative deamination The present study was supported partially by the National of a variety of amine neurotransmitters, and then the by- Science Council (no. NSC91-2320-B-273-001) in Taiwan.
product H2O2 will be generated. H2O2 is widely believed to There is no conflict of interest that we should disclose.
be one of the sources of oxidative stress and induces physio-logical peroxidation. To summarise the results of the increasedserum total antioxidant capacity and decreased organ lipid per- oxidation, it can be claimed that both the inorganic and organic Benedetti SM & Dostert P (1989) Monoamine oxidase, brain Se supplements can positively affect the improvement of the aging and degenerative diseases. Biochem Pharmacol 38, physiological antioxidative status. By preventing physiological peroxidation, brain MAO-B activity was kept from increasing Jossan SS, Gillberg PG, d’Argy R, Aquilonius SM, Langstrom during the study period. In addition, it is interesting to note B, Halldin C & Oreland L (1991) Quantitative localization of that rat brain MAO-B activity exhibited a decrease in the human brain monoamine oxidase B by large section autoradio- T group. There are few studies that indicate the effect of toco- graphy using L-[3H]deprenyl. Brain Res 547, 69 – 76.
pherol supplementation in MAO-B activity. In our opinion, this Nicotra A, Pierucci F, Parvez H & Senatori O (2004) Mono- is the first demonstration that tocopherol supplementation is amine oxidase expression during development and aging.
effective in decreasing MAO-B activity in rat brain. a-Toco- pherol is an isoform of lipid-soluble vitamin E, and is well Saura J, Luque JM, Cesura AM, Da Prada M, Chan-Palay V,Huber G, Loffler J & Richards JG (1994) Increased monoamine known as an antioxidant. It seems therefore reasonable to oxidase B activity in plaque-associated astrocytes of Alzheimer assume that tocopherol conducts these effects via protecting brains revealed by quantitative enzyme radioautography. Neuro- tissue peroxidation. The further mechanisms remain to be investigated. However, rat liver MAO-B activity exhibited a Sherif F, Gottfries CG, Alafuzoff I & Oreland L (1992) Brain non-significant difference among the groups. In g-aminobutyrate aminotransferase (GABA-T) and monoamine brain MAO activity has a positive correlation with brain and oxidase (MAO) in patients with Alzheimer’s disease. J Neural liver lipid peroxidation, but there is no correlation between Transm Park Dis Dement Sect 4, 227 – 240.
liver MAO activity and brain or liver lipid peroxidation. This Knoll J (1993) The pharmacological basis of the beneficial may be due to the reason of different functions between brain effects of (-)deprenyl (selegiline) in Parkinson’s and Alzhei- MAO (for amine neurotransmitters transformation) and liver mer’s diseases. J Neural Transm Suppl 40, 69 – 91.
Alafuzoff I, Helisalmi S, Heinonen EH, Reinikainen K, Halli- MAO (for foreign amine compounds detoxification)(42).
kainen M, Soininen H & Koivisto K (2000) Selegiline treatment We also investigated the influence of lipid peroxidation and and the extent of degenerative changes in brain tissue of patients total antioxidant capacity on brain MAO activity with Alzheimer’s disease. Eur J Clin Pharmacol 55, 815 – 819.
shows that physiological lipid peroxidation has a posi- Guay DR (2006) Rasagiline (TVP-1012): a new selective mono- tive correlation with brain MAO activity, but serum total anti- amine oxidase inhibitor for Parkinson’s disease. Am J Geriatr oxidant capacity has not the same correlation with brain MAO Rayman MP (2000) The importance of selenium to human Crosley LK, Meplan C, Nicol F, Rundlof AK, Arner ES, Hesketh JE & Arthur JR (2007) Differential regulation of expression of Combs GF Jr (2005) Current evidence and research needs to cytosolic and mitochondrial thioredoxin reductase in rat liver and support a health claim for selenium and cancer prevention.
kidney. Arch Biochem Biophys 459, 178–188.
Uthus EO & Ross SA (2007) Dietary selenium affects homocys- Ryan-Harshman M & Aldoori W (2005) The relevance of sel- teine metabolism differently in Fisher-344 rats and CD-1 mice.
enium to immunity, cancer, and infectious/inflammatory diseases.
Can J Diet Pract Res 66, 98 – 102.
Jiang C, Jiang W, Ip C, Ganther H & Lu J (1999) Selenium- Ip C (1998) Lessons from basic research in selenium and cancer induced inhibition of angiogenesis in mammary cancer at prevention. J Nutr 128, 1845 – 1854.
chemopreventive levels of intake. Mol Carcinog 26, 213–225.
Finley JW (2006) Bioavailability of selenium from foods. Nutr Sayar K, Ugur M, Gurdal H, Onaran O, Hotomaroglu O & Turan B (2000) Dietary selenium and vitamin E intakes alter b-adrenergic Tapiero H, Townsend DM & Tew KD (2003) The antioxidant response of L-type Ca-current and b-adrenoceptor-adenylate role of selenium and seleno-compounds. Biomed Pharmacother cyclase coupling in rat heart. J Nutr 130, 733 – 740.
Wu Q, Huang K & Xu H (2003) Effects of long-term selenium Fairweather-Tait SJ (1997) Bioavailability of selenium. Eur J deficiency on glutathione peroxidase and thioredoxin reductase activities and expressions in rat aorta. J Inorg Biochem 94, Qin S, Gao J & Huang K (2007) Effects of different selenium sources on tissue selenium concentrations, blood GSH-PX Danesi F, Malaguti M, Nunzio MD, Maranesi M, Biagi PL & activities and plasma interleukin levels in finishing lambs.
Bordoni A (2006) Counteraction of adriamycin-induced oxidative Biol Trace Elem Res 116, 91 – 102.
damage in rat heart by selenium dietary supplementation. J Agric Vendeland SC, Deagen JT, Butler JA & Whanger PD (1994) Uptake of selenite, selenomethionine and selenate by brush Schneider C (2005) Chemistry and biology of vitamin E. Mol Nutr border membrane vesicles isolated from rat small intestine.
Kiray M, Uysal N, Sonmez A, Acikgoz O & Gonenc S (2004) Schweizer U, Brauer AU, Kohrle J, Nitsch R & Savaskan NE Positive effects of deprenyl and estradiol on spatial memory and (2004) Selenium and brain function: a poorly recognized liai- oxidant stress in aged female rat brains. Neurosci Lett 354, son. Brain Res Brain Res Rev 45, 164 – 178.
Chen J & Berry MJ (2003) Selenium and selenoproteins in the Budni P, de Lima MN, Polydoro M, Moreira JC, Schroder N & brain and brain diseases. J Neurochem 86, 1 – 12.
Dal-Pizzol F (2007) Antioxidant effects of selegiline in oxidative Batcioglu K, Karago¨zler AA, Ozturk IC, Genc M, Bay A, stress induced by iron neonatal treatment in rats. Neurochem Res Ozturk F & Aydogdu N (2005) Comparison of chemopreven- tive effects of vitamin E plus selenium versus melatonin in El-Demerdash FM (2001) Effects of selenium and mercury on the 7,12-dimethylbenz(a)anthracene-induced mouse brain damage.
enzymatic activities and lipid peroxidation in brain, liver, and blood of rats. J Environ Sci Health B 36, 489 – 499.
Sian J, Gerlach M, Youdim MB & Riederer P (1999) Parkinson’s Ognjanovic´ BI, Markovic´ SD, Pavlovic´ SZ, Zikic´ RV, Stajn AS disease: a major hypokinetic basal ganglia disorder. J Neural & Saicˇic´ ZS (2007) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective Jana S, Maiti AK, Bagh MB, Banerjee K, Das A, Roy A & effect of selenium Physiol Res (Epublication 25 April 2007).
Chakrabarti S (2007) Dopamine but not 3,4-dihydroxy phenyla- El-Demerdash FM (2004) Antioxidant effect of vitamin E and cetic acid (DOPAC) inhibits brain respiratory chain activity by selenium on lipid peroxidation, enzyme activities and biochemi- autoxidation and mitochondria catalyzed oxidation to quinone cal parameters in rats exposed to aluminium. J Trace Elem Med products: implications in Parkinson’s disease. Brain Res 1139, Raciti G, Mazzone P, Raudino A, Mazzone G & Cambria A Doraiswamy PM & Xiong GL (2006) Pharmacological strat- (1995) Inhibition of rat liver mitochondrial monoamine oxidase egies for the prevention of Alzheimer’s disease. Expert Opin by hydrazine-thiazole derivatives: structure – activity relation- ships. Bioorg Med Chem 3, 1485 – 1491.
Castano A, Ayala A, Rodriguez-Gomez JA, de la Cruz CP, Zhang J & Piantadosi CA (1991) Prevention of H2O2 generation Revilla E, Cano J & Machado A (1995) Increase in dopamine by monoamine oxidase protects against CNS O2 toxicity. J Appl turnover and tyrosine hydroxylase enzyme in hippocampus of rats fed on low selenium diet. J Neurosci Res 42, 684 – 691.
Nagatsu T & Sawada M (2006) Molecular mechanism of the Cao G, Alessio HM & Cutler RG (1993) Oxygen-radical absor- relation of monoamine oxidase B and its inhibitors to Parkin- bance capacity assay for antioxidants. Free Radic Biol Med 14, son’s disease: possible implications of glial cells. J Neural Niehaus WG & Samuelsson B (1968) Formation of malonalde- Youdim MB & Bakhle YS (2006) Monoamine oxidase: isoforms hyde from phospholipid arachidonate during microsomal lipid and inhibitors in Parkinson’s disease and depressive illness.
peroxidation. Eur J Biochem 6, 126 – 130.
Br J Pharmacol 147, Suppl.1, S287 – S296.
McEwen CM Jr & Cohen JD (1963) An amine oxidase in Mandel S, Weinreb O, Amit T & Youdim MB (2005) normal human serum. J Lab Clin Med 62, 766 – 776.
Mechanism of neuroprotective action of the anti-Parkinson Lowry OH, Rosebrough NJ, Farr AL & Randall RJ (1951) drug rasagiline and its derivatives. Brain Res Brain Res Rev Protein measurement with the Folin phenol reagent. J Biol Sagi Y, Drigues N & Youdim MB (2005) The neurochemical Jacobs M & Forst C (1981) Toxicological effects of sodium and behavioral effects of the novel cholinesterase-monoamine selenite in Sprague – Dawley rats. J Toxicol Environ Health 8, oxidase inhibitor, ladostigil, in response to l-dopa and l-trypto- phan, in rats. Br J Pharmacol 146, 553 – 560.

Source: http://www.vivalife.com.tw/nutraceutical/image/Both%20inorganic%20and%20organic%20selenium%20supplements%20can%20decrease%20brain.pdf