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VOLUME
Vol.05 Issue06 2025
PAGE NO.
20-25
10.37547/ijmscr/Volume05Issue06-04
The Therapeutic and Biological Role of Zinc and Vitamin
D-3 In Children's Dermatology
Rikhsiev Ulugbek Shavkatovich
PhD, Associate Professor, Department of Skin and Venereal, Children's Skin and Venereal Diseases, Tashkent Pediatric Medical
Institute, Uzbekistan
Received:
14 April 2025;
Accepted:
10 May 2025;
Published:
12 June 2025
Abstract:
Our work reflects aspects of the study of the role of zinc and vitamin D-3 based on literature analysis.
Keywords:
Dermis, function, layers, complications, vitamin.
Introduction:
The skin is the largest human organ,
consisting of water, proteins, fats and minerals. It
protects against microbes, regulates div temperature
and water balance. The structure of the skin includes
three main layers: the epidermis, dermis and
subcutaneous layer.
The skin consists of three main layers: the epidermis,
dermis and subcutaneous fat, which, in turn, consist of
several internal layers.
Skin appendages such as hair follicles, sebaceous
glands, and sweat glands also help the skin perform its
functions.
Lifestyle and external factors such as solar radiation
and temperature changes have a destructive effect on
collagen and elastin, as well as on the structure of the
extracellular matrix.
As we age, our natural production of collagen and
elastin slows down, and our skin's ability to retain
moisture decreases. Skin loses tone and wrinkles
appear. Learn more about what factors affect skin
condition, why sun protection is needed, and how skin
ages.
In the human div, the most important condition for
maintaining homeostasis is the effective performance
by the skin of at least two of its most important
functions: barrier, preventing the penetration of
foreign substances from the external environment into
the internal environment of the div, and
thermoregulatory,
ensuring
the
temperature
constancy necessary for the normal functioning of the
div.
Numerous studies over the last three decades of the
biological properties of vitamin D indicate its diverse
effects on the human div. Vitamin D receptors have
been found in all organs and tissues of the human div,
which has led to the discovery of its non-calcemic
(extraosseous) effects.
Research results have proven that a sufficient level of
vitamin D in the div prevents various diseases and
pathological conditions not only in the musculoskeletal
system, but also ensures the effective functioning of
the endocrine, cardiovascular, immune and other
systems.
The studies conducted have shown that vitamin D
deficiency occurs among people of different age
groups, both in infants and young children, and in
adolescents, and including adults and the elderly. In
infants and young children, vitamin D deficiency is one
of the leading causes of rickets, as vitamin D is
necessary for the formation and maintenance of the
skeletal system. Intensive growth of young children,
high rate of skeletal modeling with insufficient intake
the presence of phosphates and calcium in the div
and the imperfections of their transport and
metabolism pathways cause the rapid development of
bone signs in infants and young children.
Although other functions of the skin (participation in
maintaining water balance, in metabolism, in gas
exchange, in immune reactions, ensuring the synthesis
of vitamin D and regulation of calcium metabolism,
protection from ultraviolet radiation, sensory function)
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play a very important role in ensuring the sustainable
functioning of the div.
It is important to take into account that the borderline
position makes the skin very vulnerable to various
external factors to which it is constantly exposed. The
skin is protected from adverse effects can only be
provided under the condition of maintaining its normal
structure and adequate ability to perform functions -
two main, inextricably linked components of the life
process of any organ and organism.
The unity of structure and function denotes the
secondary nature of functional disorders in relation to
the corresponding morphological changes at various
levels, from the organismic to the microstructural and
biochemical.
Thus, the full functional activity of the skin as an organ
is possible only on the basis of its normal structure. In
providing this condition, in addition to genetic factors
and the regulatory system, the state of the circulatory
system plays a crucial role. The effect of zinc on
physiological barriers has also been studied.
A striking example of zinc deficiency is enteropathic
acrodermatitis, which combines severe skin lesions and
diarrhea syndrome. As for the permeability of the
gastrointestinal mucosa, zinc is able to regulate the
formation of cAMP and cGMP, which activate protein
kinase C.
In zinc deficiency, the process of protein kinase
phosphorylation leads to dephosphorylation of myosin
light chains, which leads to a reduction in enterocyte
size and an increase in paracellular permeability.
In addition, zinc inhibits cAMP-induced chloride-
dependent fluid excretion by inhibiting potassium
channels, so when it is deficient, the secretion of
chlorides and water into the intestinal lumen increases.
During periods of exacerbation of the inflammatory
process in the intestinal mucosa, the need for zinc
increases (the microelement is mobilized from the
blood), which ensures reparation and intensive
renewal of the intestinal epithelium. Also, A.S. Prasad
in his studies indicates an increase in the level of
enzymes of the brush border of enterocytes when using
zinc in conditions of diarrhea.
If the human div does not receive enough zinc,
changes occur in the immune system. Thus, the activity
of thymulin, which is produced in the epithelial cells of
the thymus and ensures the maturation of
lymphocytes, decreases.
It is also necessary to note the decrease in phagocytic
activity, chemotaxis of macrophages. Precursors of B-
lymphocytes practically do not suffer from zinc
deficiency, since the level of their growth factor
interleukin 4 (IL-4) does not decrease. With a significant
deficiency of this element and a block in the
development of cells in the bone marrow, the number
of B-lymphocytes decreases.
Myelopoiesis also suffers with prolonged zinc
deficiency
and
increased
production
of
glucocorticosteroids, and the number of neutrophils
decreases. Zinc is essential for DNA replication
processes, as it plays a role in the functioning of more
than 100 transcription factors. Zinc affects the activity
of key enzymes at the basic stages of replication and
transcription.
These include DNA polymerases, thymidine kinase,
DNA-dependent
RNA
polymerase,
aminoacyl
transcriptase, RNA synthetase. A whole group of
transcriptional regulators contain Zn-containing
protein domains in their structure, known as "zinc
fingers". Zinc also increases the level of insulin-like
growth factor 1 - somatomedin, which is synthesized in
the liver under the influence of somatotropic hormone.
Insulin-like growth factor 1 stimulates DNA replication
(which is manifested by increased incorporation of
thymidine into DNA), transcription, and translation in
tissues that are targets of somatotropic hormone.
Somatomedin deficiency leads to growth disorders in
children.
The effect of reduced zinc concentrations on hormone
levels has been proven: the activity of thymulin, a Zn-
binding peptide produced by thymus epithelial cells,
decreases. The role of thymulin is to ensure
maturation, cytotoxicity, and IL-2 production by T-
lymphocytes outside the thymus.
Zinc deficiency activates the hypothalamic-pituitary-
adrenal system, which leads to hyperproduction of
glucocorticosteroids, which cause apoptosis of T-
lymphocyte precursor cells, thereby reducing their
number.
Thymus involution occurs: in experiments conducted
on mice that were given a zinc-free diet for 4 weeks, a
reduction in thymus size to 25% of the original was
demonstrated.
A decrease in the number of CD73 molecules, a
membrane enzyme necessary for lymphocyte
differentiation, was also noted on cytotoxic
lymphocytes. T-lymphocytes, especially immature
ones, die without factors survival
–
IL-
2, interferon γ,
colony-stimulating factor and zinc. When studying zinc
deficiency in an experimental model, a decrease in the
content of interferon γ and tumor necrosis factor
produced by type 1 T-helpers was found, and an
unchanged amount of IL-4, IL-6, IL-10 produced by type
2 T-helpers, i.e. an imbalance of Th1/Th2 arose.
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Zinc levels affect the activity of phospholipase C,
protein kinase, lymphocyte kinase, which are necessary
for the maturation of peripheral lymphocytes in the
thymus gland and their activation. This microelement
can increase the levels of specific antibodies (this effect
was shown in patients with shigellosis).
Zinc is a powerful antioxidant, preventing lipid
peroxidation processes and thus protecting cell
membranes from reactive oxygen species.
Formation of organic peroxides is the result of
activation of free-radical oxidation reactions in
biological systems, the main substrate of which are
unsaturated fatty acids of membrane phospholipids.
Activation of lipid peroxidation reactions is one of the
biological mechanisms of damage to biostructures and
development of cellular pathology.
Zinc is a powerful antioxidant, as it is part of superoxide
dismutase, which catalyzes the reaction of superoxide
dismutation into hydrogen peroxide and molecular
oxygen. In addition, zinc stabilizes protein structures,
preventing the combination of iron and copper ions
and the emergence of a "site of cyclic radical
formation" through multiple oxidations.
Iron and copper ions act as reversible electron donors.
The microelement also has an indirect effect on
antioxidant protection
–
by increasing the level of
metallothioneins in the liver, kidneys, and intestines.
The antioxidant properties of metalloproteins have
been proven in radiation injuries and the use of
antitumor drugs.
Zinc is able to block the synthesis of nitric oxide induced
by IL-1, as well as suppress the activity of the nuclear
transcription factor NF-kB. As a result, the production
of IL-
8, tumor necrosis factor α and other mediators of
the inflammatory process decreases.
An important property of zinc is the stabilization of
basophil and mastocyte cell membranes due to the
formation of compounds with thiol groups of plasma
membrane proteins. In addition to its effect on the
immune system, zinc has a direct antiviral effect. Zinc
salts inhibit the replication of rhinoviruses,
poliomyelitis virus, enterovirus, and herpes simplex
virus.
By binding to the surface structures of the virus, zinc
prevents its interaction with the intercellular adhesion
receptors ICAM-1. Zinc is involved in the induction of
apoptosis in virus-transformed cells.
Zinc deficiency in children increases the risk of
pneumonia, malaria, tuberculosis, measles, etc. At the
same time, a decrease in resistance to the herpes
simplex
virus,
Salmonella
enteritidis,
Lysteria
monocytogenes, Candida albicans, Toxoplasma gondii
has also been proven.
The use of zinc in these diseases is justified and,
according to L.E. Gaulfield, R.E. Black (2004), can save
the lives of 406 thousand children with pneumonia and
207 thousand children with malaria worldwide every
year.
Based on the above effects on the immune system, it
can be assumed that additional zinc administration is
advisable in various infectious diseases. The success of
such practice has already been confirmed in patients
with malaria, tuberculosis and lower respiratory tract
infections.
According to WHO and UNICEF recommendations
(2004), zinc preparations should be included in
treatment protocols for diarrheal diseases. According
to research, zinc use reduces mortality from diarrhea
by 23% in children under 5 years of age.
In addition, the use of zinc also has a preventive effect
- it reduces the likelihood of diarrhea in the next 2-3
months. It has been shown that adding zinc to oral
rehydration solutions has a beneficial effect.
However, excessive zinc intake in humans is also
harmful, as it may be associated with Zn-induced
copper deficiency. In particular, it is known that zinc
administration at a dose of 300 mg/day for 6 weeks
leads to a decrease in chemotaxis, phagocytic activity
of neutrophils and lymphocyte response.
Zinc is one of the microelements that are essential for
the human div. The daily requirement for zinc in
infants is 3-5 mg/day, in adults - 10-25 mg/day. Zinc
enters the div with food; its main source is animal
protein (meat, fish, eggs, cheese, milk), as well as
mushrooms, nuts, legumes, grains, but due to the
presence of phytic acid in the latter, the absorption of
zinc is significantly reduced. Zinc absorption occurs
mainly in the small intestine, with the help of
metallothioneins.
It should be noted that breast milk contains a low-
molecular zinc-binding ligand, which increases the
absorption of zinc by the child's div. Also, the
intestinal absorption of zinc is increased by the
presence of vitamin A, amino acids (lysine, cysteine,
glycine) in food, and calcium, iron, and copper reduce
it. Zinc is excreted from the div mainly with feces
(90%), as well as urine and sweat. It should be noted
that zinc does not accumulate in the div with age if it
is consumed in excess 48% of the world's population is
at risk of developing zinc deficiency conditions. Zinc
deficiency condition (ZDC) occurs when the zinc
concentration in the blood decreases to less than 13
μmol/l, and a zinc level of less than 8.2 μmol/l is
considered prognostically unfavorable.
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According to the conclusion of IZINCG (International
Zinc Nutrition Consultative Group), zinc deficiency in
the div correlates with growth retardation in school-
age children, the prevalence of which > 20% is
considered elevated and may indicate a problem of zinc
deficiency in the population.
According to WHO data from 2000, in Ukraine this
indicator is at the level of 22.9%. Premature babies,
children with low birth weight, HIV-infected people,
patients with chronic kidney diseases, as well as
children weakened by other chronic diseases suffer
especially from zinc deficiency.
There is a classification of CDS by time of occurrence
(A.A. Zhavoronkov, 1991), according to which CDS that
arose in the antenatal and postnatal periods is
distinguished. Studies have shown that children born to
mothers with zinc deficiency in the div had congenital
heart and brain defects in 13-18% of cases.
They also had a decrease in the mass of the spleen,
thymus, and impaired functional activity of
lymphocytes. In the postnatal period, endogenous and
exogenous zinc deficiency are distinguished, including
iatrogenic and technogenic. The first group -
endogenous deficiency - includes congenital diseases:
enteropathic acrodermatitis and sickle cell disease
anemia. Exogenous deficiency may be of alimentary
origin (Prasad's disease); secondary to gastrointestinal
tract, liver, kidney diseases; in pregnant women, etc.
Iatrogenic zinc deficiency occurs with unbalanced
nutrition, long-term treatment with cytostatics, L-
histidine. Technogenic zinc deficiency is a consequence
of excess of its so-called competitors in the
environment - lead, cadmium, chromium.
According to the classification of R. Henkin, R.L. Aamodt
et al. (1983), acute, chronic and subacute forms of CDS
are distinguished. The acute form occurs rarely, with
unbalanced parenteral nutrition; the chronic form is
typical for people whose usual diet contains few
products containing zinc (for example, true
vegetarians).
Its morphology and functional activity determine the
provision of all skin components with material
resources necessary to maintain their normal vital
activity, oxygen supply, energy and full participation in
thermoregulation. Any disturbances in the blood
supply to the skin lead to structural changes in its
components
from
functional-compensatory
to
pathological(reversible
and
irreversible).
Underestimation of the role of deviations in the blood
supply system in the development of dermatoses leads
to insufficient understanding of their etiological and
pathogenetic mechanisms and, ultimately, hinders the
prevention, early diagnosis and effective treatment of
skin diseases.
In addition, it is necessary to take into account that the
blood and lymphatic vessels of the skin are not isolated,
but are part of the vascular system of the div and the
blood supply to the skin directly depends on the state
of the cardiovascular system as a whole.
In practice, few people think about secondary
hemodynamic, and therefore trophic disorders in the
skin, arising against the background of heart pathology
or damage to the main vessels, creating conditions for
the development of many skin diseases.
There is virtually no information about the possible
prevention of these disorders, their role and
significance in the pathogenesis of skin diseases, as well
as when prescribing therapy, which naturally affects its
effectiveness and safety.
On the other hand, many skin and systemic diseases are
basically vascular in nature with predominant damage
to the microcirculatory bed of the skin and mucous
membranes, and the overwhelming majority of
dermatoses are accompanied by pronounced changes
in the microcirculatory bed of the skin, but the
mechanisms of formation of these changes in most
cases remain unexplored,
and their role in pathogenesis is underestimated and is
not always taken into account when prescribing
therapy. The reason for insufficient attention to the
vascular component in the development of skin
pathology and the obvious underestimation of vascular
mechanisms in the pathogenesis and therapy of
dermatoses and systemic diseases with involvement of
skin and mucous membranes is the lack of safe,
effective and accessible methods of objective
assessment of the circulatory bed of the skin. Such
widely used methods of vascular examination as
ultrasound examination, as radiocontrast methods are
able to effectively assess the state of the main blood
flow.
Then the assessment of the intradermal vascular
network, which performs primarily a nutritional
function, is closely connected with the vital activity of
all structural components of the skin and is of direct
interest for understanding the processes occurring in
the skin, remains beyond the capabilities of the
indicated methods.
Meanwhile, the need to study microcirculatory
processes in the skin is very relevant not only for
dermatology, but also for other medical specialties:
angiology, cardiology, rheumatology, endocrinology,
neurology, combustiology, etc.
Thus, there is evidence that the level of structural
changes and the degree of development of
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microangiopathies in the skin in diabetes mellitus are a
reflection of metabolic, vascular, neurological and
immune disorders and allow us to assess the depth of
these disorders.
Some authors have demonstrated the dependence of
biochemical processes and the general molecular
profile of the skin in diabetes on the level of systemic
disorders, and a meta-analysis conducted by Fuchs D.
et al. demonstrated a statistically significant
relationship between the level of metabolic disorders
in diabetes and dysfunction of the skin vessels.
There is evidence that the severity of some athological
changes in the skin can serve as an indicator of the
severity of the overall vascular lesion, in particular, as
an indicator endothelial dysfunction, microvascular
complications and early stages of atherosclerotic
transformation of blood vessels, and in some cases act
as an independent risk factor for the development of
atherosclerosis of the carotid arteries.
Thus, due to the availability of skin as an optimal object
for research, the creation of easily implemented,
reliable and informative methods for assessing the
morphological state of the skin and its vascular bed
could contribute, on the one hand, to understanding
the microcirculatory mechanisms of pathogenesis of
cardiovascular, endocrine, neurological and other
diseases, and on the other hand
–
early detection of
prognostically important structural changes in the skin
and diagnosis of angiopathies in various types of
systemic pathology in order to organize timely
prevention of irreversible vascular complications.
As for combustiology and surgery, the tactics and
effectiveness of treating burn surfaces and wounds
directly depend on the depth of damage to the skin and
its vascular bed, so the creation of optimal objective
methods for assessing the degree and effective
monitoring of these injuries will be of decisive
importance in the successful development of these
medical areas.
Until recently, the main and practically the only
objective method for studying the structure of the skin
and its microcirculatory bed was biopsy. The main
advantage of the histological method is the ability to
study the structure of tissue, in particular the skin, at
the cellular level, which provides high information
content, which can be increased by using, in addition to
standard special staining methods, various techniques,
including injection of vessels for their better
visualization.
The main disadvantage that prevents its widespread
use and limits its capabilities in studying the vascular
bed of the skin is its invasiveness.
Traumatization of tissue during biopsy sampling is
inevitably accompanied by disturbances in the
structure of the microcirculatory bed and ischemia,
which can distort the actual state of the vessels.
Subsequent fixation, preparation of sections and
staining can radically change the architecture of the
vascular bed and lead to an erroneous assessment of
its conditions. In addition, this method completely
excludes the possibility of studying the functional state
of the vessels, which is often necessary for the most
complete understanding of the nature of the process,
and is capable of providing only static information
corresponding to the histological picture frozen at the
time of biopsy sampling.
Due to its invasiveness, biopsy practically excludes
multifocal and repeated studies, which are necessary in
some cases for accurate diagnosis and understanding
of the underlying cause of the process. For the same
reason, it seems difficult to conduct functional tests,
dynamic observations of the development of certain
processes and assessment effectiveness and the risk of
developing side effects from the therapy. Although, in
the literature there are individual reports, mainly
concerning the study of the mechanisms of healing and
the effectiveness of therapy for burn wounds based on
the use of repeated biopsy, but all of them concern
exclusively experimental studies carried out in
laboratory conditions on simulated burn wounds using
animals. In addition, the invasiveness of the biopsy
study suggests a high risk of developing various
complications (bleeding, severe pain, infectious
complications, systemic reactions, delayed healing),
residual
tissue
deformation
and
numerous
contraindications (coagulation pathology, acute
inflammation in the lesion, manifestations of
pyoderma and systemic infectious processes,
intolerance to anesthetics, etc.). It is precisely because
of the high risk of residual deformation and technical
difficulties in taking a biopsy, even in cases of urgent
need, that a biopsy is practically impossible in such
complex localizations of the process as the corner of
the eye, eyelid, face, nail apparatus, genitals, etc. And
among some contingents (children, pregnant women,
elderly patients, patients with disorders coagulation,
diabetes, etc.), the intervention turns out to be
extremely undesirable or even impossible. At the same
time, it must be recognized that the use of biopsy for
dynamic observations and monitoring of structural
changes in tissue, even with the availability of technical
capabilities, cannot ensure the accuracy of the results,
since. When examining each new biopsy, the
esearcher observes new structures each time, while
the original object of study is irretrievably removed
when taking the first and subsequent biopsies.
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Thus, zinc, vitamin D3 is important for the growth and
development of the child's div, the functioning of the
immune system, antioxidant protection, and the
activity of all organ systems. Zinc deficiency in children
leads to delayed growth and development, and
increases the risk of various infections.
Thus, summing up the literature review, it can be noted
that the problem of skin pathologies remains an open
question.
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