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. 184.108.40.206) 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 firstname.lastname@example.org
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.
Lashkar-e-Taiba Attacks in Jammu & KashmirA. Mannes2,3, J. Shakarian2, A. Sliva1,2,3,4 and V.S. Subrahmanian1,22Institute for Advanced Computer Studies & 3School of Public Policy4 Northeastern University, Boston, MA 02115. Abstract—Lashkar-e-Taiba (LeT for short) is one of the deadli-a much larger number—over 2,000—of such rules) usingest terrorist groups in the world. With ove
ABSTRACT Keywords: bee products, antibiotics apitherapy, sulfonamides, heavy metal contamination, imunoenzymatic assay (ELISA), RIA CHARM II assay, TETRASENSOR, high performance liquid chromatography (HPLC), liquid chromatography with mass spectrometry The doctoral thesis “ Quantitative correlation of heavy metals and antibiotics in melliferous flora, honey and bee product, established