Research on the Mineral Selenium
The following research abstracts
are presented to reflect the findings of possible benefits from
minerals as a dietary supplement and nutritional supplement.
You will find more on the ionic
selenium page.
Biological Trace Element Research
(USA), 1997, 56/1 (31-41)
Serum selenium
levels were determined cross-sectionally in 57 HIV- infected
patients who were classified according to the Centers for Disease
Control (CDC) 1993 classification system. Mean serum selenium
levels were lower in CDC stage II (58.7 plus or minus 12.2 microg/L;
P <0.01; n="18)" and stage III (47.6 plus or minus
11.3 microg/L; P < 0.01; n="19)" HIV-infected patients,
than in healthy subjects (80.6 plus or minus 9.6 microg/L; n="48)"
and stage I patients (73.6 plus or minus 16.5 microg/L; n="20)."
Serum selenium levels were positively
correlated with CD4 count, CD4/8 ratio, hematocrit, and serum
albumin (r="0.42;" r="0.39;" r="0.48;"
and r="0.45;" P < 0.01, respectively) and inversely
with serum levels of thymidine kinase (r="-" 0.49;
P < 0.01; n="49)" and beta2-microglobulin (r="-"
0.46; P < 0.001; n="49)." In addition, serum selenium
levels in 20 randomly selected AIDS-free individuals (CDC I:
n="10;" CDC II: n="10)" were inversely correlated
with serum concentrations of interleukin-8 (IL-8) and soluble
tumor necrosis factor receptors (sTNFR) types I and II. There
was no correlation with serum immunoglobulin A and total serum
protein levels. The results show that the progressive deprivation
of serum selenium in HIV- infection
is associated with loss of CD4+-cells and with increased levels
of markers of disease progression and inflammatory response.
J. NUTR. IMMUNOL. (USA), 1994,
3/1 (41-49)
An important role for selenium
in immune processes has been described, with selenium
appearing to affect non-specific immune indices, humoral immunity,
cell-mediated immunity and cytotoxicity. Whereas low plasma
selenium levels have been correlated
with decreased natural killer (NK) cell activity, as well as
proliferative response of lymphocytes to mitogens in vitro,
supplementation with selenium has
been associated with enhanced lymphocyte response to phytohemagglutinin
(PHA) and pokeweed (PWM) and with enhanced NK activity when
administered in physiological ranges, but not at pharmacological
doses. The investigation of selenium
status in HIV-1 infection is of particular interest, in light
of studies documenting low plasma selenium
levels and decreased glutathionine peroxidase activity in adult
patients with AIDS. Moreover, alterations in selenium
levels have been associated with immune dysregulation in early
HIV-1 infection. As examination of pediatric nutritional status
in HIV-1 disease has been restricted in scope, this study was
designed to characterize selenium
status and examine its relationship to immune function, in HIV-1
infected children.
CHEM.-BIOL. INTERACT. (Ireland),
1994, 91/2-3 (165-180)
Deficiency in antioxidant micronutrients
have been observed in patients with AIDS. These observations
concerning only some isolated nutrients demonstrate a defect
in zinc, selenium, and glutathione.
An increase in free radical production and lipid peroxidation
has been also found in these patients, and takes a great importance
with recent papers presenting an immunodeficiency and more important
an increase in HIV-1 replication secondary to free radicals
overproduction. We have assessed different studies, trying to
obtain a global view of the antioxidant status of these patients.
In adults we observe a progressive decrease for zinc, selenium,
and vitamin E with the severity of disease, except that selenium
remains normal at stage II. However, the main dramatic decrease
concerns carotenoids whose level at stage II is only half the
normal value. To understand if these decreases in antioxidant
and increases in oxidative stress occur secondary to the aggravation
of the disease or, conversely, are responsible for it, we undertook
a longitudinal survey of asymptotic patients. The preliminary
results of this evaluation are presented. Paradoxically, lipid
peroxidation is higher at stage II than at stage IV. This may
be consecutive to a more intense overproduction of oxygen free
radicals by more viable polymorphonuclear (PMN) at the asymptomatic
stage. The free radicals production and lipid peroxidation seem
secondary to a direct induction by the virus of PMN stimulation
and cytokines secretion. N-Acetyl cysteine or ascorbate have
been demonstrated in cell culture to be capable of blocking
the expression of HIV-1 after oxidative stress and N-acetyl
cysteine inhibits in vitro TNF-induced apoptosis of infected
cells. In regard to all these experimental data, few serious
and large trials of antioxidants have been conducted in HIV-infected
patients, although some preliminary studies using zinc or selenium
have been performed. In our opinion it is now time to evaluate
in humans the beneficial effect of antioxidants. The more promising
candidates for presenting synergistic effects when associated
with N-acetyl cysteine seem to be beta-carotene, selenium
and zinc.
Archives of Toxicology (Germany),
1996, 70/5 (277-283)
The eukaryotic transcription
factor NF-kappaB is involved in the inducible expression of
various inflammatory genes as well as in HIV-1 replication.
Activation of NF-kappaB is induced by prooxidants and several
stimuli eliciting oxidative stress, such as cytokines, lipopolysaccharide,
UV irradiation and other mediators. Various antioxidants inhibit
NF-kappaB activation in response to these stimuli. In this study,
we have investigated the effects of selenium,
an integral component of glutathione peroxidase (GPX), on NF-kappaB
activation. In selenium-deprived
Jurkat and ESb-LT lymphocytes, supplementation of selenium
led to a substantial increase of GPX activity. Analysis of DNA
binding revealed that NF-kappaB activation in response to TNF
was significantly inhibited under these conditions. Likewise,
reporter gene assays using luciferase constructs driven by the
HIV-1 long terminal repeat showed a dose-dependent inhibition
of NF-kappaB controlled gene expression by selenium.
The effects of selenium were specific
for NF-kappaB, since the activity of the transcription factor
AP-1 was not suppressed. These data suggest that selenium
supplementation may be used to modulate the expression of NF-kappaB
target genes and HIV-1.
Z Gesamte Inn Med (GERMANY) May
1993, 48 (5) p223-32
Our investigations carried out
in patients with diabetes mellitus revealed oxidative stress
loads. The study presented here was to clarify whether a therapy
with antioxidants can contribute to an improvement of prognosis.
80 patients affected with a long term diabetic late syndrome
were randomised and arranged to 4 groups of n = 20 each. In
contrast to a control group these patients received 600 mg of
alpha lipoic acid or 100 micrograms of selenium
(sodium selenite) daily or 1200 IE of D-alpha-tocopherol respectively
for a time of 3 months. In comparison with the control group
all groups treated in an antioxidative way showed significantly
diminished serum concentrations of thiobarbituric acid reactive
substances and of urinary albumin excretion rates. The symptoms
of distal symmetric neuropathy measured according to the thermo-
and vibration sensitivity also improved in a highly significant
manner. The results prove that oxidative stress plays a promoting
role in developing of long term diabetic late complications
and that a therapy with adjuvant antioxidants may lead to a
regression of diabetic late complications.
Biomed Environ Sci (UNITED STATES)
Jun 1994, 7 (2) p109-15
The activities of glutathione
peroxidase (GSH-Px), glutathione reductase (GSSG-R), superoxide
dismutase (SOD) and the contents of malondialdehyde (MDA) and
free radicals were measured, and the morphological changes were
observed in the lens of control rats, selenium-deficient
(SeD) and/or vitamin E deficient (VED) rats. The activities
of GSH-Px in the lens of SeD rats decreased significantly. The
GSH-Px activities of lens were positively related to erythrocytes
selenium level. There was a free
radical at g = 2.0015 in the rat lens of all groups, but the
content of free radicals in the lens of SeD group was significantly
higher than that of the control group. The free radical content
of lens was negatively related to erythrocytes selenium
level, as well as the GSH-Px activities in the lens. In vitro,
ultraviolet radiation caused the generation of another kind
of free radical (g = 2.0097) in the lens of all groups, but
the amount of the free radical in the lens of the SeD group
was also significantly higher than that of the control group.
The activities of SOD and GSSG-R in VED rat lens were significantly
decreased. The amount of MDA in the lens of SeD and/or VED rats
were significantly increased. The results showed that the decrease
of antioxidative capability in the lenses of SeD and/or VED
rats accelerated the lipid peroxidation and generation of free
radicals. Although only early morphological changes in SeD and/or
VED rat lens were observed, it is considered that selenium
and vitamin E deficiency may be involved in the occurrence of
cataract.
Current Opinion in Rheumatology
(USA), 1995, 7/6 (497-502)
Skeletal muscle involvement may
occur at all stages of HIV infection. The most simple classification
of muscular disorders in HIV-infected patients is 1) HIV-associated
myopathies, 2) zidovudine myopathy, 3) HIV wasting syndrome,
and 4) opportunistic infections and tumoral infiltrations of
muscle. Immunohistology for major histocompatibility complex
class 1 antigen and histochemical reaction for cytochrome c
oxidase are helpful in correctly classifying a myopathy as HIV
polymyositis or zidovudine myopathy. Studies of cytokine expression
in HIV-infected patients and of supplementation with compounds
such as carnitine or micronutrients such as selenium
might yield new insights into the pathogenesis and treatment
of the various AIDS- associated muscular disorders.
Nutrition Clinique et Metabolisme
(France), 1996, 10/2 (69-76)
Adriamycin-induced cardiotoxicity
could be due to free radical formation, which induces lipid
peroxidation and membrane damage. We have studied the effect
of oral supplementation with selenium
(Se) and/or vitamin E (Vit. E) on myocardiopathy in rats treated
by adriamycin (ADM). Animals were divided into groups by ADM
(ADM) or NaCl 0.15 M solution (Control group = C); standard
diet (SD); ADM I and C I; SD with Se; ADM II and C II; SD with
Vit. E; ADM III and C III; SD with Se and Vit. E; ADM IV and
C IV. All rats received ADM or saline solution by the intraperitoneal
route. Ascitis and survival were observed throughout 18 weeks
and hearts were studied histologically. Survival was 100% for
controls while median survival was 12 (ADM I and II), 14 (ADM
III) and 16 weeks (ADM IV) in treated rats. Ascitis was significantly
less marked in ADM IV compared with ADM I (p = 0.02). Heart
weight was decreased in ADM I, II and III compared with those
of controls (p = 0.001) while it was similar to controls in
ADM IV. Cardiac lesions studied by semi-quantitative histology
were less severe in ADM IV. Se associated with Vit. E could
prevent cardiac toxicity induced by ADM treatment and may be
helpful to clinicians in chemotherapy using anthracycline.
Cancer Lett. 1994 Jul 29. 82(2).
P 153-65
Naturally occurring anticarcinogens,
such as vitamins C and E, and the microelement selenium
were found to inhibit the induction of benzo[a]pyrene-induced
malignant tumors in Wistar rats to various extends. The antineoplastic
effect of the tested anticarcinogens is gradually increased
according to the number of inhibitors selected. To date the
maximum action against malignancy is manifested by use of the
above three inhibitors. In the group of rats receiving vitamins
C, E and selenium, the prolongation
of life induced by adding more than one anticarcinogen to the
treatment regime reached, and in some cases surpassed, the normal
life expectancy of the rats. It is expected that by adding even
more anticarcinogens, the antineoplastic potency (Ap) of the
inhibitors will be further improved. These results encouraged
us to conduct a clinical trial in terminal human cancer cases,
in conjunction with the usual treatments of surgery or chemotherapy
and irradiation.
Support Care Cancer. 1993 Nov.
1(6). P 295-7
The potential of a high intake
of fresh fruits and vegetables in cancer prevention is well
established. Epidemiological studies support carotene, vitamins
A, C, E and selenium as the active
compounds. Antioxidant properties and direct effects (e.g. inhibition
of N-nitrosamine formation or cell-to-cell interactions) are
invoked. The role of other trace elements is less clear. The
modulation of immune function by vitamins and trace elements
remains important and affects survival. In established cancers,
the site-specific differences in the diet/cancer relation require
appropriate dietary changes, e.g. low fat (20% by energy) in
breast cancer, or high vegetable or fruit intake in lung cancer.
Single high-dose supplements (e.g. vitamin C) have proved to
have no curative or life-prolonging effect. Chemotherapy and
radiation increase the requirements for antioxidant compounds.
Supplementation can diminish the damage induced by peroxidation.
Carefully planned and monitored trials that establish the optimal
intake of micronutrients as adjuvants in cancer patients are
required.
