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ACCUMULATION AND EFFECTS OF ARTIFICIAL FOOD COLORANTS
E171 AND E173 IN THE BRAIN
Oysara Zaripova
Nematov Jakhongir
nematovjahongir30@gmail.com
Department of Pathological Physiology,
Bukhara State Medical Institute, Bukhara, Uzbekistan.
https://doi.org/10.5281/zenodo.16440370
Abstract.
Today, the lifestyle of mankind, the increase in living conditions,
social welfare, the improvement of working conditions, and the increase in
annual income require the development of all sectors of society. In particular, in
the manufacturing industry, the quality of the product and uniqueness, color,
packaging, and long-term storage are highly valued by consumers, in addition to
the shelf life. Food additives are actively used in industry on a large scale in
order to fully meet the above requirements. In particular, artificially synthesized
food dyes are attracting entrepreneurs with their low cost and stability. Artificial
dyes, which are very convenient to use in industry and have many advantages,
are completely replacing natural coloring agents. The fact that synthetic dyes
available in the manufacturing industry seriously affect health indicators shows
how urgent the issue is. At present, the number of diseases associated with poor
nutrition is steadily increasing. This issue is one of the key global priorities
under the attention of the World Health Organization. Therefore, in order to
prevent such diseases, the development of programs aimed at promoting
healthy eating and limiting the consumption of processed and semi-processed
food products, as well as colorful items enriched with artificial additives, is
gaining importance in the state policy designed to meet the needs of modern
society. Among the artificial food additives used to alter the organoleptic
properties of food products, food colorants occupy a significant place. These
additives are organic compounds not found in nature, i.e., they are synthetically
produced, and almost all of them have been used in the global food industry for
decades. Unlike natural colorants, synthetic food dyes do not possess biological
activity and do not contain flavoring substances or vitamins. Nevertheless, they
have important technological advantages over natural dyes: they are less
sensitive to processing and storage conditions and provide bright, easily
reproducible colors. Typical representatives of such artificial, metal-containing
food dyes are E171 and E173, which contain titanium dioxide and aluminum,
respectively. This scientific research specifically studies the effects and
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accumulation of the nanoparticle-sized titanium dioxide (E171) and aluminum-
based (E173) food dyes in the brain.
Keywords:
food colorants
,
E171, titanium dioxide, E173, aluminum,
accumulation, blood-brain barrier, nanomaterials
Inrtoduction:
nutrition is one of the key factors determining human health
and is closely linked to lifestyle and the socio-economic status of an individual
within society. Rational and balanced nutrition plays a fundamental role in
maintaining internal homeostasis, shaping the div's adaptive capabilities, and
ensuring the optimal functioning of physiological systems. When nutrition is
poorly structured in terms of both composition and quality, it can become a
major contributing factor in the etiopathogenesis of gastrointestinal pathologies,
hepatobiliary system diseases, endocrine dysfunctions, and musculoskeletal
disorders. According to data from the World Health Organization (WHO), among
diseases related to dietary factors, cardiovascular pathologies account for 61%,
neoplasms for 32%, and type II diabetes for 5% [1]. These diseases remain
among the leading causes of death in economically developed countries.
Nowadays, the use of food additives is considered a necessary condition for
industrial-scale food production. These substances can be natural, artificially
synthesized, or their compounds, and are selectively added to food products or
raw materials to achieve various technological purposes. However, products
containing such additives can pose serious health risks to humans.
It is appropriate to discuss the negative impact of certain food additives on
lifestyle and health, particularly on children and middle-aged individuals, who
are the most exposed to these substances. The concern is not limited to acute
poisoning or the absence of allergic symptoms, but also extends to the long-term
consequences of such exposure, including carcinogenic, mutagenic, and other
biological effects. The effects of food additives on public health service users are
still insufficiently explained, especially regarding the changes that occur over
time (such as mutagenicity, carcinogenicity, etc.). Only through long-term
research can accurate and comprehensive information on these effects be
obtained. According to recent findings, the titanium dioxide additive found in the
food colorant E171 contributes to tumor formation and progression by inducing
inflammation, activating immunological responses, altering cell cycle processes,
and modifying cancer-related signaling pathways. These conclusions are
significant in the ongoing discussions regarding the safety of E171 and may help
identify the molecular mechanisms related to its potential genotoxicity and
carcinogenicity. Additional toxicological studies are required to assess the safety
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of E171 and other metal-based nanomaterials used as food additives or in
packaging materials [7].
Like other fine-particle food additives, titanium dioxide is mainly found in
food products. It is found in large quantities in carbonated drinks, various
colored sweets, packaged salty and fatty crackers, potato chips, paper candies,
pastries, dairy and cheese products, and sausage products.[1]
Titanium dioxide is actively used not only in the food industry, but also in
the pharmaceutical industry, in the production of personal hygiene products,
and cosmetics as a bleaching agent. Titanium dioxide is a water-insoluble
substance with low toxicity. [2]
In the div, titanium accumulates in the form of proteins. Enterally
administered titanium dioxide interacts with the aggressive environment of the
stomach significantly affecting the properties of proteins and enzymes changes.
In a laboratory study, chronic (90 days) enteral administration of titanium
dioxide to rats resulted in spleen damage, thrombocytopenia, lymphopenia,
decreased hemoglobin levels, and decreased immunoglobulin levels.[4]
In another laboratory study, administration of titanium dioxide at a dose of
10 mg/kg resulted in severe liver damage, nephron apoptosis, and impaired
immunoregulation.
When titanium dioxide was administered enterally at a dose of 100 mg/kg
for 10 days, it was found that CD4 lymphocytes increased in all areas of the
intestine, and the secretion of cytokines IL-4, IL-12, IL-23, and TNF increased
mainly in the colon wall.[5]
Many studies have been devoted to the effects of titanium dioxide on the
div, especially on the lungs, and the changes that occur in it. In this, solutions
were sought to the questions related to the entry of small-sized titanium dioxide
through the respiratory tract in the workplace and the development of
pathological processes. Experiments conducted on rats with high doses of
titanium dioxide for two years showed that tumors developed in the lungs of the
rats, which indicated the carcinogenic properties of titanium dioxide.[6]
Fine-particle titanium dioxide, which enters the div through the
intratracheal route, damages the cellular structure of alveolar macrophages and
leads to impaired function. In addition, it reduces the chemotoxic properties of
alveolar macrophages. Small amounts of titanium dioxide increase the
phagocytic properties of macrophages, while large amounts reduce this
property. With an increase in the amount of fine-particle titanium dioxide, the
production of NO and TNF increased, since more pro-inflammatory mediators
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were synthesized under the influence of fine-particle titanium dioxide than with
conventional titanium dioxide.[7] Small amounts of titanium dioxide increased
the sensitivity of the upper respiratory tract by twofold, and the number of cells
responsible for inflammation increased by up to threefold. Histological
examination revealed edema, epithelial destruction, and inflammation [8].
Free titanium dioxide causes denaturation of cytoplasmic proteins [9].
E 173 Aluminum is one of the most common elements on Earth, ranking
third after oxygen and silicon. Aluminum compounds occur in nature in a variety
of forms. Aluminum compounds are part of more than 280 minerals and are
actively used in various fields of human activity. Despite the widespread use of
aluminum compounds, their negative consequences remain one of the most
important and necessary problems of modern medicine. In particular, its
complications related to the brain are the cause of much discussion. There is still
much debate about whether Alzheimer's disease, autism, Parkinson's disease,
multiple sclerosis, and similar profound changes in the brain are caused by
aluminum and its compounds. (11) Aluminum in drinking water, inhalation and
food products despite entering in large quantities through mucous membranes
in small quantities reabsorption occurs. luminum is not essential for the human
div and metabolic processes (13). This element has a strong toxic effect on the
div and the brain. The many ways in which aluminum enters the div and its
widespread use further emphasize its toxic properties.[11,12,13].
This toxic effect is especially pronounced in Alzheimer's disease, autism,
progressive sclerosis, and other brain dysfunctions. The attention of
international scientific journals has been focused on aluminum and the above-
mentioned neurological diseases. [12]
The main part of aluminum enters the div through water, food dyes and
used in packaging, preparation, and storage of food products enters through the
details. Unprocessed food products the amount of aluminum in its composition
is less than 5-7 mg/g. Aluminum entering the div with water is 0.3%, and with
food - 0.1%. The daily intake of aluminum is 15 mg / day[14].
E 171 and E 173 are used as food dyes and give the product a white color.
The fact that these dyes can change the analeptic properties of the product is
very useful for entrepreneurs. But there is another side to the matter. All food
additives, including food dyes that give color, can cause various pathological
reactions in the div. processes are developing[6].
This article aims to demonstrate the effects and accumulation of the
bleaching dyes E 171 and E 173 (when taken in large quantities) on the brain.
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The active substances of these dyes are: titanium dioxide (171) and aluminum
(E 173). The effects of titanium dioxide and aluminum substances on the
nervous system, including the brain, have been proven in numerous
experiments. For example, titanium dioxide powder was given to experimental
rats for a long time and changes in the brain were observed. When the EEG of
the rat brain was performed, it was observed that active epileptic foci appeared
in the brain and the rats became very aggressive. [1], [2], [3]. Aluminum is
believed to be one of the main causes of neurodegenerative diseases:
Alzheimer's disease, Parkinson's disease, autism [4], [5].
Material and methods:
We
will study the extent to which titanium and
aluminum accumulate in the brain, and how this accumulation is related to
changes in the brain . White, inbred rats selected for the experiment will be
divided into 4 groups:
1. Control group
2. Group that received E171
3. Group that received E173
4. The group that received E171 and E173
The above group of rats was given enteral titanium dioxide and aluminum
in the form of powder.
The standard for determining the mass amounts of macro- and
microelements in the researched samples is carried out in relation to samples
with known amounts of elements.
Instrumental neutron activation analysis
It was shown that for 90 days,
laboratory white rats were fed with food dyes E171 (TiO ₂- titanium dioxide)
and E173 (Al, aluminum) and the following results were obtained. The rats that
received food dyes as an experiment were divided into 3 groups:
Group I E171 (titanium dioxide) was given 500 mg/kg orally per day for 90
days as an experiment . Our instrumental neutron activation analysis revealed
that the test sample contained an average of 3.63 mg of titanium dioxide in the
dry mass of the brain trace amount of titanium (Ti) was detected. In the brains
of rats selected for control, this amount was 0.28 mg.
Group II was also given 500 mg/kg of food dye E173 (Al – aluminum) to
laboratory white rats for 90 days as an experiment. In our instrumental neutron
activation analysis, the test sample contained an average of 4.21 mg of
aluminum in the dry mass of the brain. Element aluminum (Al) was detected in
the amount of 0.53 mg/kg in the control group rats.
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Group III E171 ( titanium dioxide) 500 mg/kg and 500 mg/kg of E173 (Al –
aluminum) food dyes orally for 90 days as an experiment . Our instrumental
neutron activation analysis showed that the study sample contained an average
of 3.7 μg / g of titanium (Ti) and 4.5 μg/g of titanium (Ti) in the dry mass of the
brain traces of aluminum (Al) elements were detected.
The results obtained in the above experimental groups, compared with the
control group, revealed differences in titanium: an average of 3.63/0.28 μg/g, 13
times more, and aluminum: an average of 4.21/0.53 μg/g, 8 times more. In
addition, in the group given aluminum and titanium at the same time, compared
with the control group, it was found that: titanium increased by 3.7/0.28 μg/g,
13.2 times, and aluminum increased by 4.5/0.53 μg/g, 8.5 times.
Conclusion:
Around the worldl
it is known that the brain has a natural
blood-brain barrier, and the peculiarity of this barrier is its selective
permeability. Accordingly, various toxic substances, poisonous products and
many types of drugs circulating in the blood cannot pass through this barrier.
However, there are exceptions, and there are 3 types of entry mechanisms for
substances that have the property of crossing the barrier : 1) slow diffusion 2)
active transport mechanism 3) endocytosis. The ability of the two food dyes
titanium dioxide and aluminum shown in the experiment to cross the brain
barrier has been proven in many experiments. If aluminum crosses the barrier
by binding to proteins through the active transport pathway, then the physical
properties of titanium dioxide help it in this way. Small particles (nanoparticles)
of size 5-100 nm can easily pass through the brain barrier and show the
property of accumulation. However, the question of how titanium enters the
brain is a matter of much debate among scientists. During the 90 days of
possible entry, it is shown that the active substances in the enterally
administered dyes (E 171 and E 173): aluminum and titanium, accumulate in the
brain to a high degree, and changes in the brain may be associated with the
degree of this accumulation.
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