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Therapeutic use of intravenous selenium in respiratory and

immunological diseases: evidence based on reviews focused
on clinical trials

Authors: Carlos Rocha Oliveira, Emille Tejo Viana, Thaina Ferreira Gonçalves,
José Roberto Mateus-Silva, Rodolfo P Vieira

DOI: 10.5603/ARM.a2022.0018

Article type: Review paper

Submitted: 2021-08-14

Accepted: 2022-01-17

Published online: 2022-01-31

This article has been peer reviewed and published immediately upon acceptance.
It is an open access article, which means that it can be downloaded, printed, and distributed freely,
provided the work is properly cited.
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Therapeutic use of intravenous selenium in respiratory and immunological
diseases: a narrative review

Carlos Rocha Oliveira et al., Selenium improves lung diseases

Carlos Rocha Oliveira 1,2,3, Emille Tejo Viana 4, Thaina Ferreira Gonçalves4, José
Roberto Mateus Silva1,2,3, Rodolfo P Vieira1,5,6,7

1
GAP Biotech, São José dos Campos, Brazil
2
Anhembi Morumbi University, School of Medicine, São José dos Campos Brazil
3
Post-graduation Program in Biomedical Engineering, Federal University of São Paulo
(UNIFESP), São José dos Campos, Brazil
4
Anhembi Morumbi University, São Paulo, Brazil
5
Post-graduation Program in Sciences of Human Movement and Rehabilitation Federal
University of São Paulo (UNIFESP), , São José dos Campos, Brazil
6
Post-graduation Program in Bioengineering, Universidade Brasil, São Paulo, Brazil
7
Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology
(IBEPIPE), São José dos Campos, Brazil

Address for correspondence: Rodolfo P Vieira, GAP Biotech, Rua Comendador Remo
Cesaroni 223, São José dos Campos – SP, Brazil, 12243-020, phone: +55 12 99141-
0615, e-mail: rodrelena@yahoo.com.br

Abstract

The oxidative stress caused by systemic inflammatory response syndrome

(SIRS), septic shock, and sepsis, is a risk factor triggering an increase in mortality in
patients diagnosed with these pathologies. Selenium (Se) is an essential mineral that has
antioxidant and cytoprotective functions, being strongly associated with the proper
functioning of intracellular metabolic processes. In this context, the present study aims
to investigate de therapeutic effects of intravenous selenium use considering pathologies
such as SIRS, septic shock, sepsis, acute respiratory distress syndrome (ARDS),
ventilator associated pneumonia (VAP), and coronavirus disease (COVID-19). This is
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an narrative literature review in which six main articles found in databases of SciELO,
PubMed, and Google Scholar, were selected and analyzed. As a result, articles were
found evidencing the benefit of Se in the inflammatory response, increasing the GPx-3
activity and decreasing the inflammatory cytokines, in addition to generating a lower
risk of VAP, shortening the hospitalization time, and mortality. Thus, Se
supplementation has beneficial evidence for acute respiratory diseases and should be
considered as a viable option as adjuvant therapy.

Key words: sodium selenite, selenium, respiratory system, immune response,

respiratory disorder

Introduction

The Selenium (Se), a vital trace element for health, may be found in organic or
inorganic forms, its inorganic states being selenide -2, elemental selenium, selenite+4, and
selenate+6 [1]. Se presents both antioxidant and pro-oxidant properties, consequently, its
deficiency may be associated with heart, muscular, and osteoarticular problems, which
may aggravate several diseases due to the reduction in the response of antioxidant
mechanisms [2]. Furthermore, studies demonstrate the risk of mortality from diseases
such as ARDS, VAP, SIRS, sepsis, septic shock, and even COVID-19, are inversely
proportional to the amount of Se found in the organism [3, 4].

The antioxidant effects of Se are related to inhibition of oxidative stress and

occurs through the incorporation of proteins through the enzyme glutathione
peroxidase-3 (GPx-3), which reduces peroxides in the organism, protecting cells against
oxidative damage [3]. On the other hand, the pro-oxidant effect of Se is given by
selenoproteins, which when activated by Se, modulate inflammatory responses through
the elimination of reactive oxygen species, beyond to regulating the activity of enzymes
involved in the biosynthesis of eicosanoids, thus modulating the signaling pathways for
expression of inflammatory genes [4]. Selenoprotein-P, for example, acts to protect the
endothelium through the regulation of several enzymes present in cells, activating the
transcription of NF-κB, which is responsible for the expression of numerous genes
linked to the inflammatory response. This also occurs in cases of septic shock, in which
there is inhibition of inflammatory cascades or even the induction of a pro-apoptotic

2
effect of circulating active cells, resulting in a decrease of inflammation caused by the
disease [2].
In general terms, SIRS and sepsis are associated with decreased plasma Se and
GPx-3 activity, in which both parameters are related to disease severity and worse
prognosis [5]. Similarly, in ARDS, it is observed a marginalization of circulating
leukocytes and activation of resident macrophages into the lung parenchyma,
characterized by increased synthesis and release of reactive oxygen species and pro-
inflammatory cytokines, dampening the antioxidant capacity t in these patients. Such
effects are also observed in cases of sepsis, SIRS, and septic shock that result from an
unspecific response of the organism against an infection, generating an exacerbated
inflammation, in which the body’s antioxidant capacity not only decreases in the lungs,
as it occurs in ARDS but also systemically and in other organs [6]. Likewise, it also
occurs in cases of COVID-19, since this disease causes an exacerbated inflammatory
response as well as a reduced endogenous antioxidant response in various parts of the
organism, suggesting that these diseases are conducive to Se supplementation to
increase their levels of antioxidant protection and consequently immune [3]
The oxidative injury involved at the beginning of the pathological processes
described previously can be treated or even prevented with Se supplementation [7].
Studies demonstrate that the supplementation of this element could result in a
significant effect on the immunological competence of these patients, as it provides
greater metabolic functionality due to its cytoprotective, antioxidant, and
immunological functions [8]. Such supplementation may be achieved through the
infusion of Se precursors, such as sodium selenite as well as selenious acid, however,
depending on the intervention and the Se precursors to be used, attention during
administration must be noted, since studies indicate the possibility of toxicity related to
the administration of high doses of Se [9, 10].
The adjuvant role of Se has been demonstrated to be beneficial both in the
treatment and prognosis of some pathologies. Se has the power to increase the
efficiency of vitamin E, improving its immunological and antioxidant activity, as this
vitamin possesses known antioxidant functions [11]. In addition, the association of Se
with vitamin C can prevent and modulate actions caused by free radicals in critically ill
patients, and consequently reduce the risk of infectious complications, by attenuating
the tissue damage and lipid peroxidation, which may, therefore, be a possible adjuvant
treatment for the diseases mentioned [12].
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 Given the possibility of the use of sodium selenite and selenious acid as
precursors forms of Se for intravenous supplementation, aiming to assist patients with
or without this element deficiency, this study is fully justified. Hence, the objective of
this research is to analyze whether Se supplementation, under different intervention
protocols and different forms of precursors, has benefits in respiratory and/or
immunological disorders.

Material and methods

Research strategy

This study is a narrative literature review, produced from secondary sources,

through bibliographic surveys based on inclusion and exclusion criteria. To search for
scientific articles, searches were performed using databases from PubMed, SciELO, and
Google Scholar, by consulting the following keywords and their combinations in
Portuguese and English: ''sodium selenite'', ''selenium '', ''immunology'', “respiratory
system”, “clinical studies” “immunological response”, “respiratory disorder”. Research,
data collection, and analysis of the articles were held in April of 2021, while the
discussion and results of the data collection occurred in May and June of 2021. The data
collection was based on a “PICO” search strategy, in which the Population consisted of
patients with immunological/respiratory disorders, such as SIRS, septic shock, sepsis,
ARDS, VAP, and COVID-19, in any severity level and regardless of age group. In the
Intervention, sources of Se were used, such as sodium selenite or selenious acid, in
parenteral therapy. As for the Control, patients who used another type of intervention
other than Se supplementation. At last, the outcome was characterized by
immunological and/or respiratory disorders improvement due to increased levels of
GPx-3 and reduction of inflammatory cytokines, additionally to a lower risk of VAP,
length of hospitalization, and mortality.

Inclusion and exclusion criteria

As inclusion criteria, were selected articles that addressed the relationship of the
use of Se in humans with immunological and/or respiratory complications, clinical trials
that associated sodium selenite as a source of Se in humans, and articles that portrayed

4
the related theme to this narrative review. Articles published in English, Portuguese,
Spanish, and those indexed and published in the databases in the last 15 years were
included. Excluded articles included those that addressed the use of Se in animals or in
vitro tests, non-controlled or non-randomized clinical articles, as well as articles that did
not involve the respiratory tract or the immune system and that related to other types of
pathology. Any characteristics that did not meet the above-mentioned inclusion criteria
were also excluded from the composition of this review.

Selection and quality evaluation

Three steps were performed for the identification and analysis of the studies. In
the first stage, the titles of studies potentially relevant to this review were read, in which
those that did not meet any of the previously decided inclusion criteria or that were
repeated, were excluded. In the second step, the abstract and introduction of each article
were read to select those that met the inclusion criteria. In the third and last stage, all
studies considered to be relevant were read, evaluated, and verified about the eligibility
and relevance of the research carried out using the JADAD and New Castle scale.
Finally, this analysis and integration of the articles were achieved descriptively,
resulting in the final studies which allowed the development of the writing of this
manuscript through the establishment of acquired knowledge.

Results

The final sample of this study consists of six articles that were selected based on
previously established inclusion criteria and analyzed to present the effect of Se infusion
in clinical use for therapeutic purposes in respiratory and immunological conditions.
Regarding the type of intervention performed, two types of compounds were found,
known as Se precursors, used in the treatment group. Studies with the same type of
compound differ due to different initial doses, time of use, and the disease in question.
Based on the survey of the types of studies, all are randomized, prospective, and double-
blind, characterizing them as clinical trials, whose results are presented and synthesized
below in Table 2.

5
To a more comprehensive organization of the manuscript, the results and discussion
session is presented based on the three forms of selenium used, sodium selenite,
selenious acid and selenium protein p.

Sodium selenite on Oxidative Stress and ARDS

The study conducted by Mahmoodpoor et al (2018) analyzed 40 adult patients

with a diagnosis of ARDS classified as moderate to severe, in which 20 patients
received 4 mg of sodium selenite intravenously on the first day, 1 mg every 12 hours per
3 days, and 1 mg per day for another 6 days. As a result, the study evidenced that the
decrease in airway resistance, an important parameter of the lung mechanics, was more
significant in the SEL (+) group, rather than in the SEL (–) group, with a mean
difference of 1.2 vs 2.9; P = 0.023. The improvement in lung compliance, another
important parameter of lung mechanics, from day 0 to day 14 was 7 ± 5 mL/cmH 2O in
the control group, whereas it was 24 ± 5 mL/cmH2O in the intervention group (P =
0.028). Although the partial pressure of carbon dioxide (PaCO 2) did not change
significantly within 14 days, arterial oxygen partial pressure (PaO 2) improved
considerably from day 0 to day 14 (P < 0.001).
According to the results, Se supplementation did not reduce inflammatory
response considerably, even taking into consideration the increase in the antioxidant
activity of GPx-3 in the lungs, it was also observed that Se supplementation did not
reduce plasma cytokines, except for interleukin 1 beta (IL-1 beta), which demonstrated
to be reduced in the Se-treated group, when compared to the control group, on the
seventh day of the intervention. Thus, it can be observed that Se supplementation has
modest modulatory effects on the inflammatory response, even if it partially restores the
pulmonary antioxidant capacity.
To amplify the strength of the study regarding the effects of Se supplementation
on mortality and length of hospitalization, study subjects were complemented with an
additional patients, in which 72 patients received Se supplementations and 67 were
pooled as controls. The results demonstrate that the duration of mechanical ventilation
was similar between the two groups, as well as the length of hospitalization. However,
11 deaths were registered in the intervention group, while in the control group a total of
16 deaths were recorded. A possible explanation, although partial, could be based on
improved pulmonary mechanics and superior recovery in patients who received Se

6
supplementation, suggesting that such supplementation exerted some modulation on
inflammation present in the lung parenchyma and small airways, in addition to
promoting an enhancement in pulmonary gas exchange rates that significantly improved
after the second week of treatment [13, 14].

Sodium Selenite on Ventilator-associated Pneumonia

Mahmoodpoor et al (2007) evaluated the effect of Se administration on the

incidence of ventilator-associated pneumonia (VAP) in critically ill patients.
Consequently, ninety-nine mechanically ventilated patients were evaluated, in which 47
patients received Se infusion in the form of intravenous sodium selenite at a dose of
3000 μg on the first day and 1500 μg on the following 9 days, as for the control group
(n = 52) received saline solution for 10 days. The results demonstrate that the serum
concentrations of Se and GPx-3 increased steadily in the supplementated group,
whereas, in the placebo group, these concentrations remained unchanged. The incidence
of VAP was relatively greater in the placebo group when compared to the Se group,
however, the risk of VAP or death was similar in both groups. These results suggest that
Se supplementation in the form of sodium selenite, by increasing the activity of GPx-3,
can exert an important antioxidant action [15]. Bouch et al. (2017) demonstrated that the
GPx-1 gene can alter pulmonary immunological parameters, which could,
hypothetically, shed light on the role of GPx-3 in potential pulmonary complications
such as VAP [16]. It is noteworthy that GPx-1 and GPx-3 levels are extremely sensitive
to changes related to Se concentrations, with a minor tendency for GPx-2 and GPx-4
levels [17]. Though the study exhibited an increase in antioxidant activity, it is possible
to infer that Se supplementation did not reduce the incidence of VAP mortality in
critically ill patients.

Sodium Selenite on Septic Shock and Sepsis

Meaux et al (2017) analyzed 60 patients with severe septic shock, in which 31

patients received 4000 μg of sodium selenite, by continuous infusion on the first day,
and 1000 μg/day in the subsequent 9 days, while the other 29 patients received placebo.
Results showed that the origin of sepsis was pulmonary, with a higher rate of
pneumonia in the Se group, as well as lung infection. Multisite infection was less
observed when compared to the placebo group. The duration of ventilation was shorter

7
in the placebo group when compared to the intervention group, indicating a significant
effect on the duration of mechanical ventilation, ICU stays, mortality rate, and
occurrence of nosocomial pneumonia. This may occur due to incipient toxicity of
sodium selenite that opposes the moderate beneficial effect of the infusion, which may
indicate that the dose used in the clinical trial was beyond the ideal dose to support the
immune defense, reinforcing the findings of other similar studies included in this
narrative review, in which lower doses of sodium selenite are used presenting beneficial
clinical outcomes [18].
Chelkeba et al. (2015) investigated the effect of Se administration as an
antioxidant, in addition to cytokine levels and clinical outcomes. 54 patients with severe
sepsis, septic shock, or being mechanically ventilated for more than 48 hours were
evaluated, in which 29 patients received 2000 μg of sodium selenite in 100 ml of saline
solution within the first 6 hours of sepsis diagnosis, followed by 1500 μg of sodium
selenite in 250 ml of saline solution for 12 hours continuously for 14 days, while the
other 25 patients received standard therapy without utilizing Se. Mortality rates were
lower in the intervention group (31%) when compared to the control group (40%), in
addition, the study observed a considerable increase in GPx-3 levels, which can block
the harmful effects of the inflammatory cytokines, even if there were other sepsis-
responsive mediators [19]. The study evidenced that SOFA and VAP decreased in the Se
group when compared to the control group, demonstrating that VAP was identified in
55.2% of Se patients and 84% of control patients, confirming that cytoprotective
properties of Se and the idea that its supplementation reduces lung infections, and
consequently, lung dysfunction. This occurs because Se increases its intracellular
concentrations, and it gradually increases GPx-3 activity, which will reduce the damage
of endothelial cells and the adherence of bacteria to the cells of the respiratory mucosa,
therefore reducing the infection [20].
On the other hand, another study by Landesberg et al. (2015) involving patients
with myocardial dysfunction and severe sepsis demonstrated a negative correlation
between inflammatory cytokines and disease severity, thus suggesting that Se has no
effect in septic patients since this element did not present any long-term effect on the
levels of pro-inflammatory cytokines [21]. As a result, a combined strategy proposal
was created, which was analyzed in a study involving 165 patients who required
mechanical ventilation due to septic conditions, and who received enteral nutrition with
omega-3, γ-linolenic oil, vitamins E and C, and omega-6 added to Se. The results

8
exhibited benefits in terms of mortality rate, oxygenation, ventilation-free days, and
organ dysfunction, suggesting an alternative and adjuvant approach to Se infusion [22].

Selenious acid on SIRS

In a study involving the administration of selenious acid, carried out by
Manzanares et al. (2011), the efficacy of Se administered by continuous infusion in
patients with SIRS was evaluated. The intervention group, consisting of 20 patients,
received high doses of selenious acid associated with a 0.9% NaCl solution through a
bolus of 2000 μg of Se for two hours, and subsequently, a bolus of 1600 μg/day with
continuous infusion and daily for 10 days, while the control group received only 0.9%
NaCl.

Selenious acid on VAP

Results indicated that early VAP was diagnosed in one patient in the selenious
acid group and six patients in the placebo group. Meanwhile, the incidence of late VAP
was similar between the groups, however, nosocomial pneumonia (28 days after
discharge from the ICU) was observed only in the placebo group, pointing out the
beneficial effects of selenious acid administration. GPx-3 activity on days 3 and 7 was
significantly different between groups (p = 0.001), yet, no statistical difference was
observed (p = 0.09) on the tenth day. In addition, GPx-3 levels gradually reduced
between days 7 and 10, even with continuous supplementation of the Se precursor. Such
reduction may be associated with insufficient production of hydrogen selenide,
selenocysteine, or limitation of glutathione (GSH) synthesis, due to shortages of
glutamine or cysteine, suggesting that depleted stores of these compounds need to be
replenished exogenously to maintain adequate GPx-3 levels for the reduction of damage
in SIRS [23].
Even with the reduction in GPx-3 activity, Se therapy was associated with a
meaningful improvement in the severity of septic shock, sepsis, and early VAP, findings
that may be associated with its immune function in inducing apoptosis and cytotoxicity
in pro-inflammatory cells, in addition to the inhibition of NF-κB binding to DNA and
direct virucidal or bactericidal effects [24]. Studies demonstrate that Se, at physiological

9
levels, can inhibit the activation of the transcription factor NF-kappa B, which is the
final common stage of the expression of pro-inflammatory cytokines, making the
modulation of their activity the target of several anti-inflammatory drugs [25]. Finally, a
study indicated that the pro-oxidant effect of selenite bolus, before continuous infusion,
has an anti-inflammatory effect, and consequently, clinical benefit, helping to elucidate
the pathogen earlier [13].

COVID-19 and Selenium

Moghaddam et al. (2020) investigated whether COVID-19 mortality risk would

be inversely correlated to Se status in the organism. Thus, blood analysis of 33 patients
with COVID-19 was performed. The criteria chosen as a reference classified a normal
state of Se between 45.7–131.6 μg/L, and 2.56–6.63 mg/L for the concentration of
selenoprotein, which indicated 44.4% of the samples of COVID-19 patients deficient
for serum Se and 39.6% of patients with COVID-19 with serum samples deficient for
selenoprotein.
When comparing the samples of patients who survived COVID-19 with those
who died, the difference was 64.7% against 70.6% of serum Se and selenoprotein
deficiency, respectively. It is noteworthy that serum Se values could have been
relatively low in these patients before COVID-19, making them more prone to virus
contamination [26, 27]. Furthermore, during disease development and after exacerbated
inflammation, pre-existing low Se levels could be further reduced, as observed in sepsis
and other severe diseases [28]. Another important aspect would be the extended stay in
the ICU under inflammatory and hypoxia conditions, which may generate a greater need
for Se due to the continuous loss of this element [29].
Considering that an exacerbated inflammatory response may be directly related
to the status of Se in the organism, it is notable that oxidative stress can overcome the
endogenous antioxidant capacity of protective selenoenzymes, such as GPx-3 and
thioredoxin reductase, in addition to low molecular weight antioxidants [30], this can be
observed through the therapeutic success with mimetic GPx-3 [31, 32]. Another study
indicated that sodium Se can oxidize thiol groups in disulfide isomerase proteins of the
SARS-CoV-2 virus, thus preventing the COVID-19 virus from penetrating the
membrane of healthy cells of its possible hosts [33]. Such hypotheses can be considered

10
about Se, since this trace element is of great importance for inflammatory diseases,
justifying its supplementation.

Selenium Toxicity and Adverse Events

By correlating doses used and adverse events, the study by Mahmoodpoor et al.
(2018) did not indicate the presence of adverse events related to the high dose of
intravenous sodium selenite and aspects of toxicity attributable to intervention doses,
likewise in the study by Manzanares et al. (2011) and Chelkeba et al. (2015). In another
study, Mahmoodpoor et al. (2017), analyzed the pulmonary antioxidant reserve of
patients with VAP, indicating minimal toxic effects, but not related to patient mortality.
Meaux et al. (2007) showed some adverse events due to high doses of Se, but also,
paradoxically, these high doses resulted in lower mortality from septic shock in patients
with SIRS. Table 3 summarizes these results.

Limitations

The studies present certain suggested limitations due to small number of studies
included in this review, differences in doses, interventions, and pathologies. Initial doses
ranged from 3000 μg to 4000 µg exhibiting different results regarding airway resistance,
lung compliance, duration of mechanical ventilation, mortality rate, GPx-3 activity,
VAP, adverse events, SOFA score, and nosocomial pneumonia. Although the
aforementioned pathologies present an inflammatory reaction that results in oxidative
stress, they differ in terms of etiology and pathophysiology. Therefore, these restrictions
can interfere in the outcomes, as well as in the discussions, and may not fully portray
such real benefits and harm of Se supplementation.

Conclusions

The review supports the beneficial use of Se and Se precursors in acute

inflammatory respiratory diseases, pointing out promising results. However, bigger
clinical trials are needed as a proof of concept of such initial findings.

Conflicts of interest

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None declared.

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Table 1. Flowchart on the selection and evaluation of scientific articles

Google
SciELO PubMed
Scholar
(n = 98) (n = 115)
(n = 135)
Identification

References found by
searching eletronic
databases (n = 348)
Review of articles

Studies excluded by
duplication (n = 146)

References to read
titles and abstracts
(n = 202)

Studies excluded after exclusion and

Evaluation and eligibility

inclusion criteria (n = 193)

• 116 included animals
• 29 referred to diaseases that were not
immunological or respiratory
• 48 were not relevant or pertinent

Selected references
for full text reading
(n = 9)

Studies excluded after

full reading of the
Inclusion

article (n = 3)

Selected articles (n = 6)

16
17
 Table 2. Articles raised in databases as results of this study and their respective results

Seleniu Intervention Diseas Results Reference

m forms e
20 patients with
ARDS  Lower airway [4]
ARDS received
4 mg of sodium resistance in the

selenite intervention

intravenously on group;

the first day, 1

 Improved lung
mg every 12
compliance, as
hours for 3 days,
well as
and 1 mg daily
PaO2/FiO2 in the
Sodium for 6 subsequent
intervention
selenite days with a total
group;
of 10 days of
intervention.  Same duration of
mechanical
ventilation
among groups;

 The shorter
length of
hospitalization,
as well as a lower
rate of mortality
in the
intervention
group.

18
47 critical and VAP  Increased serum [15]
mechanically Se levels and
ventilated GPx-3 activity in
patients received the treatment
3000 μg group, increasing
intravenously on during the
the first day and intervention;
1500 μg on the
following 9  Lower risk of

days, totaling 10 VAP in the

days of intervention

intervention. group, although it

has the same
incidence in both
groups.

31 patients with Septic  There was no [10]

septic shock shock significant
received difference in
continuous mortality rates,
intravenous 400 adverse events,
μg on the first duration of
day, and 1000 mechanical
μg per day on ventilation, ICU
the subsequent 9 stay, and the
days, with a occurrence of
total nosocomial
intervention pneumonia;
period of 10
days.  Longer
mechanical
ventilation time
in the

19
 intervention
group.

29 patients with Sepsis,  The lower death [19]

sepsis, severe severe rate in the
sepsis, or septic sepsis, treatment group;
shock, received and
2000 μg septic  Higher levels of

intravenously shock GPx-3 and

within the first 6 cytokines in the

hours of sepsis treatment group

diagnosis for 1 in the last days of

hour, followed intervention;

by 1500 μg for
 Significant
12 hours
reduction in
continuously for
SOFA and VAP
14 days, being
scores in the
observed for 28
treatment group;
days.

 Diagnosis of
early and late
VAP, lower in the
intervention
group.

20
 20 patients with SIRS  Lower diagnosis [9]
SIRS received of early VAP in
Selenio
an initial bolus the intervention
us acid
dose of 2000 μg group and equal
for 2 hours, and rates of late VAP
continuous 1600 diagnosis in both
μg daily for 10 groups;
days, under
observation for  Nosocomial

28 days. pneumonia only

in the control
group;

 Decrease in
SOFA score in
the treatment
group;

 Higher level of
GPx-3 activity in
the intervention
group.

19 patients COVI  Deficiency of Se [3]

diagnosed with D-19 in 44.4% and of
Seleniu
COVID-19 had selenoprotein P
m,
their blood in 39.5% of
selenopr
samples patients with
otein P,
analyzed for COVID-19;
and
biomarkers:
GPx3 in  Of the deceased
plasma Se,
plasma patients, 64.7%
selenoprotein P,
and GPx-3 were deficient in

activity, all Se and 70.6%

deficient in
21
 patients had selenoprotein P,
their clinical significantly
outcomes and higher when
compound compared to
amounts patients who
compared. survived the
disease;

 Recovery of Se
levels in
surviving patients
when compared
to the day of
hospital
admission.

ARDS — acute respiratory distress syndrome; COVID-19 — coronavirus disease;

GAPx3 ― glutathione peroxidase 3; ICU — intensive care unit; PaO2/FiO2 ― oxygen
partial pressure/inspired oxygen fraction ratio; Se ― selenium; SIRS ― systemic
inflammatory response syndrome; SOFA — sequential organ failure assessment; VAP
— ventilator associated pneumonia

Table 3. Comparison of doses and adverse effects

Selenium Dosage Disease Adverse events Reference

forms
The initial dose of 4 mg of
sodium selenite intravenously on
the first day, 1 mg of sodium
selenite every 12 hours for 3
days, followed by 1 mg daily for
ARDS Some adverse events such [4]
as nausea, vomiting, and
changes in the nail bed.
Patients have no adverse
reaction related to the high

22
Sodium another 6 days.
selenite
The initial dose of 3000 μg on
the first day and 1500 μg in the
following 9 days, using 3 mg of
Se as sodium selenite in 100 mL
of isotonic saline solution as an
initial bolus in the first 3 hours of
mechanical ventilation, followed
by 1.5 mg of Se in 100 mL of
isotonic saline solution at the
same interval of one hour daily
for the other 9 days of
mechanical ventilation.
The initial dose of 4000 μg
sodium selenite on the first day
as a bolus, and 1000 μg/day in
the 9 subsequent days by
continuous intravenous infusion.
The initial dose of 2000 μg of
sodium selenite in 100 mL of
saline solution within the first 6
hours of sepsis diagnosis,
intravenously for 1 hour,
followed by 1500 μg of sodium
selenite in 250 mL of saline
solution for 12 hours
continuously for 14 days.
dose of intravenous sodium
selenite.
VAP Studies evidenced that [15]
none of the deaths within
the group of patients who
received Se
supplementation were due
to the iatrogenic effects of
drug therapy.
Septic shock Adverse events were [10]
similar in both groups and
were an increase in Se
Toxicity at doses above
0.35 mg/kg
Sepsis, The study did not evidence [19]
severe any adverse events or
sepsis, and toxicity at these high doses
septic shock of Se.
23
 The initial dose of selenious acid SIRS
Selenious with a bolus of 2000 μg of Se for
acid 2 hours and 1600 μg of Se per
day in continuous and daily
infusion for the following 10
days.
The study did not evidence [9]
symptoms of acute toxicity
and incidence of adverse
events attributable to this
dose of sodium selenite.
24
25