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This paper presents materials on the study of the embryotoxic effect of the antibacterial drug "Doxycycline-complex", which includes: doxycycline hyclate - 100 mg/ml and bromhexine hydrochloride - 5 mg/ml, and lactulose - 100 mg/ml and soluphor – up to 1 ml. The studies were carried out on 2 groups of non-linear virgin rats (n=15 in each group) with an initial weight of 230–250 g. The first group of animals (control) received a solvent containing soluphor and the excipients bromhexine and lactulose at the rate of 100 mg/kg body weight, the second group (experiment) received the drug “Doxycycline-complex” at a dosage of 100 mg/kg of animal body weight (10 mg/kg for the active substance - doxycycline hyclate). Calculation of embryotoxic effect indicators was carried out according to the methodological recommendations of the State Pharmacological Committee (“Guide to experimental (preclinical) study of new pharmacological substances”, Moscow, 2005). Based on the results of autopsies of animals, the following indicators were determined: the number of corpora lutea, the number of implantation sites, the number of live and dead fetuses, data on pre-implantation and post-implantation death of fetuses was recorded, the craniocaudal size of fetuses was measured, an external examination of fetuses was carried out and the number of fetuses with developmental anomalies was determined. studied the state of the skeletal system and the state of the internal organs of the fetuses, in particular, recorded the number of examined fetuses with developmental anomalies. Based on the data obtained, it was established that the study drug “Doxycycline-complex” has embryotoxic properties and has a negative effect on the offspring during the initial period of pregnancy.

bromhexine

embryotoxicity

antibiotics

doxycycline hyclate

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Introduction

The primary attention of the scientific community is paid to the search for new antimicrobial agents or their combinations that have comprehensive preventive and therapeutic potential, allowing to reduce the risk of side effects and implement full-fledged therapy. Particular importance is attached to reducing the toxicity of drugs and increasing their bioavailability.

It is known that almost all antibacterial drugs have an embryotoxic effect; accordingly, experimental study of the long-term consequences of exposure to chemicals on the body is an essential section of the toxicological and hygienic assessment of drugs. In the complex of biological effects related to the long-term consequences of exposure to chemical factors, it is important to study the influence of chemical compounds in the prenatal period of development of the organism. Currently, numerous data have been accumulated on the possible influence of chemicals on the processes of embryogenesis.

Identification of the real and potential danger of the harmful effects of chemicals on the fetus in experimental conditions on laboratory animals requires unified methodological approaches for the selection of test objects, test doses, duration of the experiment and quantitative assessment of the results. The generally accepted concept of embryotoxicity implies the potential for a substance to have a negative effect on the offspring during the initial period of pregnancy, i.e. during the period between conception and embryo formation.

Considering the widespread, and not rare and uncontrolled, use of broad-spectrum antibacterial drugs in livestock and poultry farming, it is necessary to pay special attention to the study of the pharmaco-toxicological properties of the chemotherapeutic drugs being developed, including the determination of embryotoxic properties.

Purpose of the study. To conduct an experimental study of the embryotoxic effect of a new dosage form of the developed drug “Doxycycline-complex” on laboratory animals.

Materials and research methods

The object under study is a combined antibacterial drug, which is a combination of the following components: doxycycline hyclate - 100 mg/ml, bromhexine hydrochloride - 5 mg/ml, and lactulose - 100 mg/ml and soluphor (polyvinylpyrrolidone) as excipients.

The studies were carried out in accordance with the “International Recommendations for Conducting Biomedical Research Using Animals” (1985), “Guidelines for the Hygienic Evaluation of New Pesticides” (Kiev, 1988), and methodological recommendations of the State Pharmacological Committee (“Guide to Experimental (Preclinical) study of new pharmacological substances", Moscow, 2005) and order of the Ministry of Health of the Russian Federation No. 267 of June 19, 2003 "On approval of the rules of laboratory practice". Experiments were carried out on outbred white sexually mature virgin (unfertilized) female rats weighing 230-260 g.

The animals were kept in a vivarium in accordance with sanitary rules and on a standard diet in accordance with the order of the USSR Ministry of Health No. 1045-73 of 04/06/73; rules of laboratory practice and order of the USSR Ministry of Health No. 1179 of October 10, 1983. The animals were kept in a vivarium under standard lighting (12 hours light/12 hours dark) at an air temperature of 20 °C and a relative humidity of 70%. Work with animals was carried out in accordance with the order of the USSR Ministry of Health No. 755 dated August 12, 1977 and the rules adopted by the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes.

The embryotoxic properties of doxycycline were studied at a dose of 10 mg/kg (therapeutic dose).

Intact sexually mature males weighing 280-350 g, mated with females for induction of pregnancy, were excluded from the experiment after confirmation of pregnancy. Before the experiment, vaginal washings were taken from each female. An animal was considered pregnant if spermatozoa were detected in the washings during microscopic examination (this day is considered the first day of pregnancy). The study of the safety of "Doxycycline complex" in the antenatal period was carried out on non-linear virgin rats of 2 groups (n=15 in each group) with an initial weight of 230-260 g. The animals were administered the following test substances: group I (control) - soluphor (solvent ), containing excipients bromhexine and lactulose - in adequate volumes (based on the volume of the drug administered to the experimental group of animals or 100 mg/kg body weight);

Group II (experiment) - the drug “Doxycycline-complex” at a dosage of 10 mg/kg of animal body weight for the active substance (Doxycycline hyclate).

The drugs were administered to the animals using a gastric tube once a day at the same time from days 1 to 19 of pregnancy. On the 20th day of pregnancy, rats were euthanized and dissected under ether anesthesia. Based on the results of autopsies of animals, the following indicators were determined: the number of corpora lutea, the number of implantation sites, the number of live and dead fetuses, data on pre-implantation and post-implantation death of fetuses was recorded, the craniocaudal size of fetuses was measured, an external examination of fetuses was carried out and the number of fetuses with developmental anomalies was determined. studied the state of the skeletal system and the state of the internal organs of the fetuses, in particular, recorded the number of examined fetuses with developmental anomalies.

After external examination and morphometry, the fruits of each litter were fixed in 96° ethanol and used to study the state of the skeleton using the Dawson method. Staining of the skeleton with alizarin (Dawson's technique, modified in the Department of Embryology of the Research Institute of Experimental Medicine of the USSR Academy of Medical Sciences). Staining of the ossified areas of the fruit skeleton was done by immersing the fruits in a weak solution of alizarin red. Then the fruits were studied, skeletal anomalies and the number of ossification points in various bone formations were taken into account. The data obtained during the necropsy of each animal were recorded.

Research results and discussion. An assessment of the state of the generative function of rats under the influence of the drug “Doxycycline-complex” did not reveal significant changes in the preimplantation death of embryos, which was 6% in the experimental group and 5% in the control group, which indicates the homogeneity of the groups of animals. At the same time, significant changes were noted in the study of post-implantation fetal death, which in the experimental group was 15.7%, which is significantly higher compared to 7.14% in the control group of animals (Table 1). These changes indicate the high embryotoxicity of the drug.

Table 1. Assessment of the state of the generative function of rats under the influence of the drug “Doxycycline-complex”

	Experienced group			Control group
	Number of live fruits	Number of dead fruits	Number of implants	Number of live fruits	Number of dead fruits	Number of implants
Average per animal
Total

An external examination of the fetuses during the autopsy of females from the experimental group who received Doxycycline Complex at a therapeutic dose revealed pathologies of the fetuses. Various deformities were observed in 47.4% of fetuses. Among the developmental anomalies, the most commonly observed were cleft palate, hypoplasia of the lower jaw, hypoplasia and syndactyly of the limbs. No evidence of fetal pathology was found in the control group. In addition, subcutaneous hemorrhages, hemorrhages in the lining of the brain, and accumulation of blood in the serous cavities were found in 47.4% of fetuses who were orally administered Doxycycline Complex (Table 2).

Table 2. Study of the embryotoxic effect of the drug "Doxycycline-complex" on white rats when administered orally

Indicators
	control
Number of pregnant females
Number of corpus lutea
Number of implantation sites
Number of live fruits
Number of dead fruits
Preimplantation death, %
Post-implantation death, % Fruit weight, g
Craniocaudal size, mm
External examination of fruits: the number of examined fruits of which with developmental anomalies:	a total of 182 fetuses were examined; no external fetal anomalies were found
Condition of the skeletal system: number of examined fetuses with developmental anomalies: abs %
Condition of internal organs: number of examined fetuses with developmental anomalies: abs %

Conclusion

A combined antibacterial drug based on doxycycline, lactulose and bromhexine has embryotoxic properties, which is confirmed by post-implantation death of fetuses (15.7%) and the occurrence of deformities in 47.4% of fetuses in the experimental group. Based on the research results, Doxycycline complex should be excluded from the number of antibiotics prescribed to animals during pregnancy and mating.

Reviewers:

Kalyuzhny I.I., Doctor of Veterinary Sciences, Professor of the Department of Therapy, Obstetrics and Pharmacology, Saratov State Agrarian University named after. N.I. Vavilova", Saratov.

Domnitsky I.Yu., Doctor of Veterinary Sciences, Professor of the Department of Morphology, Animal Pathology and Biology, Saratov State Agrarian University named after. N.I. Vavilova", Saratov.

Bibliographic link

Sazykina K.I., Volkov A.A., Staroverov S.A., Larionov S.V., Kozlov S.V. STUDYING THE EMBRYOTOXIC ACTION OF THE ANTIBACTERIAL DRUG “DOXYCYCLINE – COMPLEX” // Modern problems of science and education. – 2014. – No. 3.;
URL: http://science-education.ru/ru/article/view?id=13302 (access date: 02/01/2020). We bring to your attention magazines published by the publishing house "Academy of Natural Sciences"

The pharmacological composition of the most effective medicines is not complete without the presence of chemicals. In this regard, many drugs can not only cure, but also cause side effects. Toxic action is an uncharacteristic response of the body to the influence of any irritants. Various unexpected symptoms can result from damage to organs, tissues and various body systems.

Causes

The following reasons may cause complications caused by taking medications:

• physicochemical composition of the drug;
• senile or childhood age of the recipient;
• the formation of decay products of toxic substances that poison the body;
• weak general condition of the patient;
• Exceeding the dosage or taking the drug incorrectly;
• combination of drugs with incompatible pharmacological properties;
• individual intolerance to one of the components of the drug, dysbiosis or allergy;
• taking illegal medications during pregnancy and breastfeeding.

The toxic effect of drugs, as a rule, spreads selectively, affecting individual organs and tissues of the body. However, its acute phase can trigger the launch of irreversible processes in several systems simultaneously.

Mechanism of action

Almost every medicinal substance (DS) causes side effects, but not all of them manifest themselves. Reactions disappear after discontinuation of the drug. However, there is a risk for the patient to develop a “drug-induced disease.”

Two main aspects that help to avoid serious consequences are compliance with medical prescriptions and following the instructions for the drug.

The mechanism of toxic action is such that the time range from the moment of taking the drug to the appearance of side effects has no clear boundaries. They can reveal themselves immediately after taking the medicine, or after several weeks, months and even years. Acute toxic effects manifest themselves sharply and in the shortest possible time. Most often, it is the patient’s liver and kidneys that suffer, since these organs are involved in filtering and removing decay products of poisons and harmful substances. Excessive stress can lead to complete dysfunction.

Embryotoxic effect

During the gestational period, the forces and resources of the mother's body are completely directed towards the development of the fetus. Although a pregnant woman and an embryo have different blood supply systems, it receives nutrition through the umbilical cord and all substances that enter the mother’s body are transported to the child. Such a concept as embryotoxic effect implies abnormal development of the fetus as a result of taking drugs prohibited during pregnancy and occurs in the first trimester.

Before the fertilized egg attaches to the placenta (the first 1-3 weeks after fertilization of the egg), medications affect its development in the lumen of the fallopian tubes and the process of its movement into the uterus. This action threatens the appearance of various deformities in the newborn. Among the drugs that can have a greater negative impact on the embryo are antimetabolites and antimycotics: colchicine, fluorouracil, mercaptopurine.

Teratogenic effect

From the beginning of the second month of pregnancy until its end, there is a teratogenic effect. It is at the end of the eight-week period from the beginning of gestation that the fetus develops the skeleton and develops internal organs. Its tissues at this moment are very sensitive to the effects of external negative factors. Congenital deformities in the form of skeletal developmental anomalies or organ failure are a consequence of the teratogenic effect of drugs that the mother took during pregnancy.

It was found that after taking strong sleeping pills and tranquilizing drugs, such as thalidomed, the child was born with improperly developed limbs shaped like flippers. Antitumor drugs and alcohol entering the female body during conception can also have a teratogenic toxic effect.

Fetotoxic effect

When pregnancy reaches 20 weeks, at this stage all systems and organs are already formed and function in the same way as in an adult. During this period, due to the use of medications, the unborn child is affected by fetotoxic effects. Anticoagulants affect the hematopoietic system, inhibiting the function of blood clotting. Sleeping pills and strong sedatives negatively affect the central nervous system. The use of ethyl alcohol, even as part of medicines, in small quantities and narcotic substances also cause reactions from the central nervous system and can lead to the development of cerebral palsy.

Mutagenic effect

Medicinal substances can have a mutagenic effect, manifested by a change in genetic information in the germ cells of both sexes and at the stage of cellular formation of the embryo.

Carcinogenic effect

The carcinogenic effect lies in the ability of the drug to cause the destruction of cells in the recipient and their absorption by neighboring tissues, which leads to the formation of malignant tumors.

Precautionary measures

Considering that the toxic effect of drugs can cause irreparable harm, the prescription of any drugs to a pregnant woman should be carried out by an obstetrician-gynecologist. This does not mean at all that nothing can be accepted in the situation. In order to avoid serious consequences, you should carefully study the instructions and composition of the product and adequately assess the ratio of benefit to the mother/risk to the fetus.

Mild herbal sedatives, vitamin complexes and folic acid can be taken during this period . However, medication should be taken under close medical supervision. An important aspect is monitoring the condition of the expectant mother and the development of the fetus using blood and urine tests.

Modern pharmacology introduces only those drugs that are not capable of having embryotoxic, teratogenic, fetotoxic, mutagenic and carcinogenic effects on the human body and on the child inside the womb.

Allergy and dysbiosis

Dysbiosis

Violation of the composition of natural microflora is also a manifestation of toxic effects. Dysbacteriosis (dysbiosis) is a lack of beneficial bacteria in the intestines, mouth and vagina, which is replaced by pathogenic and fungal organisms. This phenomenon is a consequence of taking antibiotics and certain hormonal drugs.

Toxic effects due to dysbiosis are manifested in the following reactions:

• from the gastrointestinal tract: frequent loose stools, abdominal cramps and pain, bloating and flatulence;
• from the female reproductive system: vaginal candidiasis, the distinctive symptoms of which are itching and white curdled discharge from the vagina;
• in case of violation of the microflora of the oral cavity: stomatitis, ulcers and wounds on the gums and palate, thrush on the tongue, increased body temperature, unpleasant odor.

To prevent such reactions, antibiotics are combined with antifungal agents (nystatin, pimafucin) and probiotics and prebiotics (bifidumbacterin, lacidophil, etc.).

Allergic reactions due to toxic effects occur against the background of the perception of drug components as antigens. The dosage in this case does not play a role and the severity of side effects varies: it can be skin rashes and anaphylaxis.

There are four types of allergic reactions:

1. Instant. Develops within several hours after taking a toxic drug. The dosage may be minimal. Immunoglobulins E react with antigens, which leads to the release of histamine. Manifestations of toxic effects can be very different: skin itching, swelling, rashes, runny nose, lacrimation, swelling of the throat and anaphylaxis. Antibiotics of the penicillin series can provoke an immediate reaction.
2. Cytotoxic. A nonspecific cell reaction caused by the production of IgG and IgM antibodies to determinants. Allergens are one's own tissues modified under the influence of drugs. Hematological diseases due to such exposure can be caused by antihypertensive drugs, sulfonamides, and antibiotics.
3. Immunocomplex. This is the result of the combined action of the allergen with IgM, IgE and IgG. The victim develops allergic alveolitis and serum sickness, the symptoms of which are itching, urticaria, and fever. This effect can be observed after taking penicillin and sulfonamide.
4. Delayed. These are skin manifestations that occur after the drug in the form of a cream, ointment, emulsion or suspension comes into contact with the skin. In addition, delayed onset of allergies may be the result of an organ transplant or rheumatism. In this case, there is no early phase; the immune system reaction immediately occurs, caused by lymphocytes and microphages.

The only way to prevent an allergy is to not take medications that cause it, and to warn your doctor about the development of an allergic reaction to a particular drug. If you are taking the medicine for the first time in your life, you should first inject it under the skin or smear it on a small area on the back of the forearm and see the result.

The toxic effect of drugs most often occurs during an overdose. Individual reactions to drugs used in medical practice occur less frequently, and allergies are usually provoked by paracetamol and penicillin. It is impossible to predict what response will follow when taking a particular drug. However, drugs such as antibiotics, tranquilizers and hormones should be taken strictly under the supervision of a doctor, so as not to start an irreversible process and not harm your health.

(based on the book by Dr. O.A. Mazur “Capillary therapy cures 95% of diseases”)

According to modern domestic and foreign medical statistics, a significant number of women have extragenital pathology at the time of pregnancy or suffer at various stages of pregnancy, that is, diseases of the extragenital area that are not directly related to the reproductive organs. According to the same data, up to 80% of women take at least one pharmacological drug during this period. On average, according to foreign experts, each pregnant woman takes 4 medications, not counting vitamins and iron supplements.

It is well known that many drugs cross the fetoplacental barrier and create real concentrations in the blood plasma of the developing fetus, which can adversely affect its development. Weakness in the function of the eliminating (removing toxins) organs of the unborn child can cause a fetotoxic (poisoning the fetus) effect when using even a medicine that is relatively harmless for an adult body. Incorrectly prescribed treatment can ruin a person’s entire future life.after his birth.

Doctors prescribing pharmacological drugs to pregnant women should know and take into account the following important points:

• main periods of intrauterine development of the body;
• embryotoxic (poisoning the embryo), teratogenic (causing deformities) and fetotoxic effects of drugs;
• metabolism (transformation in the body) of medications in pregnant women;
• passage of drugs through the placenta and amniotic fluid;
• metabolic characteristics of the developing fetus;
• the main periods of intrauterine development and the effects of drugs on the unborn child.

As is known, the human body in the initial period of its development goes through three stages:

1. Period of blasto- and embryogenesis;
2. Fruit development period;
3. Newborn period.

Therefore, medications used by a pregnant woman can cause three types of effects on the body of the unborn child: embryotoxic, teratogenic and fetotoxic.

Embryotoxic effect

The embryotoxic effect occurs in the first three weeks after fertilization of the egg and consists in the negative effect of drugs on the zygote and blastocysts located in the lumen of the fallopian tubes or in the uterine cavity (before implantation of the fertilized egg into it) and feeding on uterine secretions. Damage and, as a rule, death of the blastocyst is caused by the following pharmacological substances: hormones (estrogens, progestogens, growth hormone, deoxycorticosterone acetate), antimetabolites (mercaptopurine, fluorouracil, cytarabine, etc.), inhibitors of carbohydrate (iodoacetate) and protein (actinomycin) metabolism, salicylates, barbiturates, sulfonamides, fluorine-containing substances, antimitotic agents (colchicine, etc.), nicotine. If the human embryo continues to develop in the mother's womb, it means that it is not damaged.

Teratogenic effect

A teratogenic effect can develop from the third to the tenth week of pregnancy (but many experts rightly suggest extending the boundaries of the dangerous period until the 12th week of pregnancy) and leads to various disturbances in the normal development of the fetus, the occurrence of anomalies of its internal organs and systems. The type of defect depends on the duration of pregnancy, on which organs are laid down and intensively formed in the embryo during the period of taking the drug. It is believed that the most dangerous period for the development of major defects, that is, for the manifestation of teratogenicity of the drug, is the 3-10th week of intrauterine development, which corresponds to approximately 5-12 weeks after the first day of the last menstruation. Consequently, teratogenic effects are most likely soon after implantation of the egg into the uterine wall, that is, when the woman often does not yet know that she is pregnant.

The likelihood of developing a defect in the fetus depends not only on the pharmacological drug prescribed to the pregnant woman, but also on her age (the likelihood increases if the pregnant woman is under 17 or over 35 years old), on her state of health, the functioning of the drug elimination (removal) organs, the dose of the drug, the duration of its appointment, genetic predisposition to the development of a particular defect.

Based on the degree of risk of developing a teratogenic effect, researchers divide drugs into three groups.

Group 1 of substances that are extremely dangerous for the developing fetus and therefore absolutely contraindicated in pregnant women include: thalidomide, antifolate drugs (methotrexate, trimethoprim, co-trimoxazole), androgens, diethylstilbestrol and hormonal oral contraceptives. It is recommended to stop taking the latter at least 6 months before the planned pregnancy.

Group 2 includes medications that are somewhat less dangerous to the fetus and are prescribed to those suffering from epilepsy, diabetes, malignant neoplasms, and some others. Chronic diseases themselves are, of course, a factor predisposing to the occurrence of a teratogenic effect. However, the potential danger of teratogenic action of pharmacological agents of this group, which includes: antiepileptic drugs (difenin, hexamidine, phenobarbital, valproic acid), alkylating antitumor drugs (embiquine, dopan, sarcolysine, chlorbutin), oral (orally administered) antidiabetic drugs, as well as ethanol (ethyl alcohol) and progesterone.

The 3rd group includes drugs that cause malformations under conditions predisposing to this: the first trimester of pregnancy, young or “old” age of the pregnant woman, high doses of the drug, etc. This group of drugs consists of: salicylates, antibiotics of the chloramphenicol and tetracycline, anti-tuberculosis drugs, quinine, imizin, fluorotane (dangerous for pregnant women - workers in anesthesiology departments), vitamin K antagonists, meprotan, neuroleptics, diuretics, anaprilin.

Fetotoxic effect

In the later stages of pregnancy, the fetal organs are mostly formed, so pharmacological agents can no longer cause large anatomical defects in it. Damage may include prematurity, tissue damage, inhibited or impaired organ function, or impaired behavioral responses. The administration of hormones, androgens or progestogens to a pregnant woman is accompanied by masculinization of the fetus. Iodide, lithium and antithyroid drugs used in large doses provoke the development of goiter. Tetracyclines interfere with the development of teeth and bones; quinolones interfere with cartilage development. Prostaglandin synthetase inhibitors (acetylsalicylic acid and indomethacin) can slow down the onset of labor and cause dysfunction of the cardiovascular system in the fetus, since prostaglandins are involved in maintaining the patency of the ductus arteriosus in the fetus, relaxing its muscles.

Fetotoxic effects occur due to an excessively pronounced and characteristic pharmacological effect on the fetus for a given drug (usually in the last weeks of pregnancy) or an undesirable effect specific to the drug. For example, administration of indomethacin to a pregnant woman results in closure of the ductus arteriosus in her fetus before labor occurs; beta-adrenergic agonists disrupt carbohydrate metabolism in the fetus; aminoglycoside antibiotics have an ototoxic effect on the fetus, that is, they affect the tissues and functions of the inner ear. Clinical experience shows that the administration of certain medications to pregnant women can lead to the development of perinatal (childbirth-related) pathology and even the death of the fetus or newborn child.

Medicines before childbirth

Medicines used on the eve of childbirth can cause negative pharmacological effects in the postnatal (postpartum) period. For example, difficulty breathing through the nose, drowsiness, and difficulty feeding a child occur when using reserpine. The antibiotic chloramphenicol causes vascular collapse and hematopoietic disorders in newborns, since it does not conjugate in them. Vasodilators provoke a decrease in blood supply to the uterus and fetus. When beta blockers are used, the fetus may not respond to hypoxia. Sulfonamide drugs displace bilirubin from its connection with plasma proteins, as a result of which the child is born with jaundice. Anticoagulants and antiplatelet agents increase the risk of bleeding. Children born to a woman addicted to opioid drugs may develop withdrawal syndrome with physical manifestations.

Children whose mothers took psychotropic drugs during pregnancy may experience mental changes due to a slowdown in the development of the central nervous system. In particular, such children may have difficulty learning in the future.

The lack of in-depth studies covering a large number of drugs does not allow clear recommendations for increasing or decreasing doses, so most pregnant women are administered drugs at normal therapeutic doses.

Medicines can enter the fetus through the placenta (transplacental route) and amniotic fluid (amniotic fluid), which it actively absorbs through its tracheobronchial tree and lungs, as well as through the gastrointestinal tract. For most pharmacological drugs, their accumulation in amniotic fluid is low, but some create significant concentrations, for example the antibiotics ampicillin and oxacillin. This property is used in the treatment of intrauterine infections of the fetus.

Features of metabolism in the fetus

An important role in the processes of metabolism (biochemical transformation) of drugs is played by the function of the liver, which in the fetus is immature both functionally and morphologically. The functional maturation of the liver in the fetus and the appearance of drug-metabolizing enzymes in it occurs in parallel with histological (tissue) maturation until the moment of birth. However, full metabolism is possible only during postnatal development. Insufficient inactivation of drugs by the fetal liver leads to the fact that a number of drugs (barbiturates, narcotic analgesics, indirect anticoagulants and many others) have a more pronounced toxic effect on the fetus than on the maternal body.

Factors that can have a harmful effect on the fetus include the following:

Hypoxia;

Overheating;

Hypothermia;

Ionizing radiation;

Organic and inorganic teratogens;

Infectious factors;

Medicinal substances.

Turning to history, we should recall some of the results of studies of the harmful effects of environmental factors on the embryo and fetus. For example, Greg showed back in 1941 that maternal illness with rubella is a teratogenic factor for the fetus. In the late 1950s, Minamata disease (mercury poisoning) emerged in Japan. Over the past 30-40 years, we have learned: the use of diethylstilbestrol (synthetic estrogen, used in the first trimester of pregnancy to treat the threat of miscarriage) during pregnancy can cause the development of squamous cell cancer of the cervix and vagina at the age of 17-18 in girls.

Epidemiological studies conducted over the past decades have identified a number of drugs with obvious teratogenic properties.

The most famous example of an epidemic outbreak of malformations caused by the action of a teratogenic drug is the case of thalidomide (1961-1962).

The administration of the antifolic substance aminopterin (previously used specifically as an abortion inducer) leads to the appearance of a characteristic syndrome of developmental defects in the fetus and termination of pregnancy.

Malformations occurred after the administration of androgens, estrogens and progestins, which have a strong effect on sexual differentiation.

Quite a large number of newborns have been reported to suffer from nasal cartilage hypoplasia and bone granulation caused by the use of the indirect anticoagulant warfarin. Cases of malformations have been observed after the use of drugs intended to treat thyroid diseases. In addition, these drugs sometimes caused goiter with hypo or hyperthyroidism in a child.

Hormonal contraceptives can cause teratogenesis with the formation of heart and limb defects. However, this applies to older hormonal contraceptives, while in modern drugs the dose of hormones is smaller, and there is no need to terminate a pregnancy after accidentally taking them.

There have been reports of cases of deafness developing in children exposed in utero to streptomycin or quinine. Glucocorticoids often contribute to cleft palate and lip (1:1000).

Tetracyclines administered to the mother at approximately 8-9 weeks of pregnancy are deposited in the bones of the fetus and inhibit bone growth in the fetus and newborn, and can also cause discoloration of teeth and the development of congenital cataracts.

The administration of salicylates has been associated with spontaneous abortion, prematurity and hemorrhagic pneumonia in the fetus, and, when used late in pregnancy, with closure of the ductus botallus.

In the last 20 years, it has become obvious: the damaging effect of drugs on the fetus is often not expressed in the occurrence of anatomical defects. Thus, the use of androgens, estrogens and progestins has sometimes led to subanatomical disorders of sexual behavior in men and women.

It should be noted: the causes of 80% of all developmental defects are still unknown; only 10-15% of them are explained by the influence of genetic and chromosomal factors. As a rough estimate, only 1-5% of birth defects are due to drugs, the rest due to something else.

The effect of a particular factor is determined by the stage of intrauterine development at which it exerts its influence, and to a lesser extent - by the nature of the factor itself.

The period of intrauterine development of a person can be divided into stages shown in Fig. 118.

Rice. 118. Stages of intrauterine development

The stage of preimplantation development begins from the moment of fertilization of the egg and continues until the blastocyst penetrates the decidua on the 7-8th day after fertilization. This period is characterized by the absence of a morphological connection between the embryo and the organs of the woman’s reproductive system, but this does not exclude a close functional connection. There is an idea about the relative resistance of the embryo at the stage of preimplantation development to the action of damaging environmental factors. Due to the pronounced ability of the morula and blastocyst for pluripotency and regeneration, various pathogenic factors (hypoxia, ionizing radiation, chemical agents, etc.) either do not cause the death of the embryo and do not disrupt the subsequent development of the fetus, or lead to its death (embryotoxic effect). This pattern is known as “all or nothing.” However, sometimes damage caused to the embryo in the preimplantation period appears later, during implantation and subsequent stages of intrauterine development.

After implantation, organogenesis and placentation begin, which are mainly completed by 3-4 months of intrauterine life. In this period, the most sensitive phase of development is the first 3-6 weeks of ontogenesis. As a result of the pathogenic action of environmental factors in the embryo and fetus, those organs and systems that are being formed at the moment are primarily affected.

After the completion of the processes of organogenesis and placentation, the fetal, or fetal, period of development begins, which in humans continues until 40 weeks of pregnancy. At this stage, embryotoxic and teratogenic effects are practically not observed; only anomalies in the development of the genital organs in female fetuses are possible, arising under the influence of androgenic drugs (false male hermaphroditism). This is due to the relatively late completion of the formation of the external genitalia of the human fetus (12-14 weeks of intrauterine development).

Numerous damaging environmental factors can exert their pathogenic effect by penetrating the placenta or by altering its normal permeability. The human placenta is of the hemochorial type, which ensures the closest contact between the blood of the mother and the fetus. The term “placental barrier” refers to the distance between the inner surface of the fetal capillary and the outer surface of the cytoplasmic membrane of the villous syncytium. The morphological substrate of the placental barrier is the epithelial cover of the villi and the endothelium of the fetal capillaries. The placental barrier does not allow many substances into the fetal bloodstream. Contact is carried out over a large area of ​​the exchange surface of the placenta - 12-14 m2.

Having limited permeability, the placenta is able to protect the fetus from the adverse effects of many toxic products that enter the mother’s body.

Environmental factors that have a damaging effect on the embryo are called embryotoxic.

Teratogenesis

The name “teratology” comes from the Greek word “teras” (translated as “monster”). The term "teratogenesis" literally means the production of freaks and deformed organisms. In recent years, this term has come to include the concept of functional abnormalities in the newborn (including intrauterine growth retardation and subsequent behavioral disorders). Almost nothing was known about teratogenesis before 1950, and the origin of most birth defects was thought to be genetic.

VPR classifications

Types of VLOOKUP

Malformation- a morphological defect as a result of an internal disturbance of the development process due to genetic factors.

Disruption- a morphological defect as a result of an external obstacle or any impact on the initially normal development process due to teratogenic factors.

Deformation- violation of the shape, appearance or position of a body part caused by mechanical influences.

Dysplasia- disruption of the organization of cells in tissue due to dyshistogenesis.

According to severity of manifestation and prognosis for viability:

Lethal malformations (0.6%) leading to the death of the child (up to 80% of children die before the age of 1 year);

Congenital malformations of moderate severity requiring surgical intervention (2-2.5%);

Minor developmental anomalies (up to 3.5%), which do not require surgical treatment and do not limit the child’s vital functions.

Depending on the duration of the harmful factors:

Gametopathies (mutations in the germ cells of parents and non-hereditary changes in eggs and sperm), realized in the form of hereditary diseases and syndromes;

Blastopathies (with damage to the blastocyst - the embryo of the first 15 days after fertilization), realized in the form of twin defects, cyclopia, etc.;

Embryopathies (occurring from the 16th day to the end of the 8th week of pregnancy and caused by the teratogenic effects of various physical, chemical, biological factors), which are almost all isolated and multiple congenital malformations;

Fetopathies (caused by damage to the fetus in the period from the 9th week to the end of pregnancy), represented by rare defects of dystopia and organ hypoplasia.

According to the anatomical and physiological principle of dividing the human body into organ systems.

1. Defects of the central nervous system and sensory organs.

2. Defects of the face and neck.

3. Defects of the cardiovascular system.

4. Defects of the respiratory system.

5. Defects of the digestive organs.

6. Defects of the musculoskeletal system.

7. Defects of the urinary system.

8. Defects of the genital organs.

9. Defects of the endocrine glands.

10. Defects of the skin and its appendages.

11. Defects of the placenta.

12. Other vices.

The pathogenesis of congenital malformation is currently quite well studied. Violation of the development of the embryo at the pre-implantation stage with reversible cell damage is characterized by their restoration, and with irreversible damage it leads to the death of the fetus. At later stages of development, replacement mechanisms for repairing damaged cells do not function; any violation can lead to the formation of defects. The embryonic period is characterized by the emergence of tissues from the cells of the embryonic rudiment and the development of organs and systems of the body, the interaction of the genome of the embryo and the mother’s body, her hormonal and immune systems, and is associated with the processes of reproduction, migration, cell differentiation and the formation of organs and tissues. Genetic control mechanisms in the later stages of embryogenesis can be disrupted under the influence of various external factors, defined as teratogens.

The main cellular mechanisms of teratogenesis are changes in reproduction (hypoplasia, organ aplasia), migration (heterotopia) and differentiation

cell recession (agenesis of organs or systems). The main mechanisms of teratogenesis at the tissue level include the death of cell masses, slowing down the decay and resorption of cells, disruption of cell adhesion processes, which accordingly leads to such defects as atresia of natural openings, fistulas and defects in tissues.

An important role in determining the causes of the development of congenital malignancies was played by pathogenetic teachings about critical and teratogenic termination periods.

Critical periods in embryogenesis coincide with periods of the most intensive formation of organs and are characterized by increased sensitivity of the embryo to the damaging effects of environmental factors. The first critical period in humans occurs at the end of the 1st - beginning of the 2nd week of pregnancy, when a damaging factor often leads to the death of the embryo. The second critical period begins from the 3rd week of pregnancy, when a similar factor induces a malformation.

Continuation of the table. 39

Embryonic period
Organogenesis
Formation of the brain and spinal cord
Laying the heart, kidneys and limbs
Rapid development of the brain, eyes, heart and
limbs
Beginning of intestinal and lung development Appearance of fingers Development of ears, kidneys, liver and muscles
Closing of the palate, formation of joints
Sexual differentiation
Fetal development (fetal period)
Perceptible movements of the eyelids
Opening of the eyelids
Increase in body weight and length

The relationship between gestational age and fetal malformations is shown in Table. 40.

Table 40

The relationship between the timing of pregnancy and the occurrence of fetal malformations

Genetic disorders

Most fetal abnormalities are the result of improper development of the fertilized egg. This development can begin at any time after conception. It has been shown that the earlier spontaneous abortion occurs, the higher the proportion of abnormal fertilized eggs. More than 70% of spontaneous abortions in the first trimester are caused by genetic and chromosomal disorders. Folic acid protects the fertilized egg (promotes its repair), therefore its use is recommended in all pregnant women at risk of developmental defects.

Electromagnetic radiation and mechanical energy

Ionizing radiation

The minimum intensity of ionizing radiation required to produce embryotoxic effects or to inhibit fetal growth is at least 10 times greater than the background radiation level. X-ray exposure of women of reproductive age should be kept to a minimum. At radiation doses >50 rad, major malformations and significant retardation of fetal growth occur, but even at a dose of several rad, the risk of developing leukemia in newborns increases significantly. There is a very high risk when using gamma-emitting radioisotopes such as I 125 and Tc 99.

Chronic exposure to microwave radiation (i.e., radar waves) has been associated with an increased incidence of Down syndrome. Ultrasound with a frequency of 1-3 MHz and an intensity exceeding 5 W/cm 2 led to an increase in embryo mortality and the incidence of malformations in experimental animals. The intensity of ultrasound used for diagnostic purposes is in the range of several mW/cm2, so it does not cause much harm, but hearing loss in children has been reported with frequent ultrasound; Doctors involved in ultrasound diagnostics gradually develop vibration disease.

Hyper- and hypothermia

Hyper- and hypothermia lead to an increased incidence of major malformations. Hyperthermia is observed during febrile states with a high temperature in the mother during pregnancy and her visits to the sauna during this period.

Infections (viral and bacterial)

The main cause of possible developmental disorders of the fetus are viral infections. Dozens of different viruses can cause an increase in fetal mortality and the incidence of major malformations. Embryotoxic or fetolytic defects are caused either directly by transplacental infection (infection with a fetal virus), or indirectly due to the febrile state of the mother. The rubella virus is the most pathogenic, especially in the first 90 days of pregnancy - it causes congenital heart defects, deafness and cataracts. Cytomegalovirus infection (transmitted sexually or via saliva) can lead to microcephaly and FGR. Coxsackievirus (enterovirus) is associated with a significant increase in the incidence of cleft lip and face, pyloric stenosis and other digestive tract abnormalities and congenital heart defects. Herpes virus type II (urogenital) can lead to microcephaly and viral (herpetic) pneumonia after birth. There is a relationship between vaccinia virus and limb and central nervous system defects; mumps virus and heart disease; influenza virus and an increase in the overall incidence of malformations in the population.

Bacterial infections can also be accompanied by a febrile state and high temperature, as well as infection of the fetus itself, especially if combined with prematurity and premature rupture of the membranes. During pregnancy, vaccines containing live microorganisms should not be used, since pregnant women have weakened immunity. There are no effective treatments for cytomegalovirus and herpesvirus infections; Mumps vaccines should also be avoided. If a pregnant woman has hepatitis, human anti-hepatitis immunoglobulin is administered; contact with a patient with hepatitis is not an indication for vaccination. When a pregnant woman comes into contact with a patient with smallpox, anti-smallpox gamma globulin is used. In polio outbreaks, pregnant women can be vaccinated with the same vaccine used in children. In general, only vaccines containing killed viruses are recommended.

Oncogenes

Oncogenes are substances that can react with DNA and modify it. The transplacental toxicity of polycyclic aromatic hydrocarbons, benzo-a-pyrene, methylcholanthrene, various triacines, nitrosourea and secondary amines has been proven. The effect of these factors is both embryotoxic and teratogenic.

Inorganic teratogens

An increase in the concentration of these substances in the body occurs during mining, metallurgical and metalworking processes. Lead is the main inorganic teratogen; it causes disorders of the central nervous system, leading to the development of mental retardation, cerebral palsy, and microcephaly. Exposure to mercury causes motor and mental development disorders in children. Cadmium, arsenic, and chromates reduce mental activity. Histological changes and enamel staining were observed on the baby teeth of children whose mothers drank spring water with a fluoride concentration 20 times higher than normal.

Other harmful environmental factors

Malnutrition (risk groups - people with low socio-economic levels; administration of vitamins and folic acid is recommended).

Poor quality products (sprouted potatoes). Contaminated drinking water.

Physical agents used in medicine, etc. Medications

A - no risk - 0.7% of drugs.

B (“best” - the best) - no evidence of risk - 19%.

C (“caution” - caution) - risk is not excluded - 66%.

D (“dangerous” - dangerous) - the risk is proven - 7%.

X - contraindicated during pregnancy - 7%.

Assess potential benefits and potential harms.

Avoid using medications in the first trimester.

Do not prescribe combinations of drugs.

Use the minimum effective dose for the minimum time.

Give preference to local dosage forms.

Advise the pregnant woman about taking any medications, including analgesics, vitamins, dietary supplements, herbal preparations and other means used for self-medication.

Monitor the intake of all medications by a pregnant woman.

Monitor the condition of the mother and fetus during drug therapy.

Many medications are addictive (withdrawal syndrome in newborns).

Alcohol and smoking

Alcohol during pregnancy in moderate quantities (less than 30 ml of ethyl alcohol per day) does not have a harmful effect on the fetus. When pregnant women consume ethyl alcohol in an amount of 30-60 ml per day, approximately 10% of children experience intrauterine growth retardation and a small number of congenital anomalies are observed. If a woman consumes >60 ml of ethyl alcohol daily, she is classified as an alcoholic; fetal abnormalities are expressed mainly in decreased birth weight and postnatal retardation

physical and mental development. The reason for the formation of alcohol syndrome in the fetus may be associated with the formation of acetaldehyde during metabolism, deficiency of B vitamins, malnutrition and a general predisposition to infectious diseases.

Smoking during pregnancy may be associated with an increased incidence of spontaneous abortions and neural tube defects. As the gestation period increases in smoking women, placental perfusion decreases, which leads to histological changes, aging of the placenta, and FGR. The frequency of placental abruption, premature birth, and preeclampsia is increasing.

Anesthetics

Local anesthesia does not create problems for the fetus. With general anesthesia, a harmful effect on the fetus can only be observed if hypoxia is allowed to develop, leading to impaired perfusion in the placenta.

Antimicrobial agents

Penicillins, cephalosporins, macrolides are not dangerous to the fetus.

It is better to exclude aminoglycosides (genta-, monomycin) as they have an otonephrotoxic effect.

Streptomycin is prescribed for tuberculosis in pregnant women if the risk of its negative effects is less than from the underlying disease.

Tetracyclines are absolutely contraindicated - they lead to disruption of the development of bones and teeth.

Sulfonamides should not be used; they interfere with the binding of bilirubin in the newborn and lead to the development of kernicterus (an irreversible change in brain function).

Nalidixic acid derivatives should not be prescribed during pregnancy; they cause hydrocephalus.

Levomycetin, used before childbirth, causes the development of “gray syndrome” in the fetus, but during pregnancy it is less dangerous for the fetus.

Metronidazole (Flagyl, Trichopolum) - it can be used from the second trimester; it is better not to prescribe the drug in the first trimester.

Antifungal drugs are not absorbed in the digestive tract and are therefore safe.

Antithyroid drugs (Mercazolil) in the fetal blood reduce the concentration of thyroid hormones.

Thyroxine does not penetrate the placental barrier; releasing factors penetrate and lead to the development of goiter.

Antiestrogens (clomiphene, clostilbegit) can promote multiple pregnancies.

Antihypertensive drugs all have side effects. The best drug is hydralazine (peripheral vasodilator).

Dopegit in hypertension can lead to hemolytic anemia and cause intestinal meconium obstruction.

β -adrenergic blockers in large doses increase the tone of the uterus and contribute to intrauterine growth retardation of the fetus.

Ganglion blockers cause paralytic ileus in the newborn.

Rauwolfia preparations cause nasal congestion and depression of respiratory function.

Nitrates (nanipruss, perlinganite) are used for controlled normotension during labor. The drugs are metabolized into cyanide, which poisons the newborn (with long-term use).

Prostaglandin synthetase inhibitors (salicylates, non-steroidal anti-inflammatory drugs) inhibit the synthesis of prostaglandins and help relieve the threat of miscarriage. Large doses in the early stages disrupt the blood coagulation system, cause respiratory distress, closure of the ductus arteriosus, and death of the fetus in the uterus.

Tranquilizers - there is no convincing evidence of their harm when used in reasonable doses. But tranquilizers should be prescribed only according to strict indications, because these drugs are addictive (withdrawal syndrome).

Note:+ - drug of choice; (+) - can be assigned; (-) - it is better not to prescribe; - - contraindicated.

Risk factors for the development of congenital malformation

Unplanned pregnancy.

Late maternal age.

Insufficient prenatal control.

Viral infections.

Taking medications with teratogenic effects.

Alcohol.

Smoking.

Drugs.

Malnutrition.

Occupational hazards.

Poor health care in many countries.

Indications for periconceptional prophylaxis of congenital malformations

Geneticist (1st meeting before pregnancy)
History, pedigree, examination, cytogenetic and other genetic studies according to indications, prognosis of offspring, recommendations for pregnancy planning and prevention of congenital malformation in the fetus
Gynecologist	Urologist/andrologist	Other specialists
History, gynecological status, study of vaginal microbial flora, hormonal and other studies, basal temperature, pregnancy planning	Spermogram, treatment of acute and chronic diseases	Somatic status, sanitation of foci of chronic infections, examination for STDs, chronic viral infections, toxoplasmosis, etc., antibodies to the rubella virus to resolve the issue of the need for immunization
Geneticist (2nd and 3rd meeting during the 1st and 2nd trimester of pregnancy)
Periconceptional treatment for women: multivitamins high in folic acid (0.8 mg) and diet for 2-3 months before conception and 2-3 months after pregnancy Prenatal diagnosis of congenital malformation and chromosomal pathology in the fetus: ultrasound examination at the recommended time, screening of maternal serum markers (AFP, hCG, unconjugated estriol), invasive diagnostic methods (if indicated) Analysis of the results of prenatal examination of the fetus and assessment of individual genetic risk for congenital malformation during this pregnancy
Geneticist (4th meeting)
Medical genetic counseling, examination of the newborn (according to indications)

Decalogue of commandments for the prevention of congenital birth defects (geneticist Eduardo Castillo, Brazil)

Any fertile woman can be pregnant.

Try to complete your family while you are young.

Carry out prenatal control in the prescribed manner.

Get vaccinated against rubella before pregnancy.

Avoid medications unless strictly necessary.

Avoid alcoholic drinks.

Avoid smoking and smoking areas.

Eat well and varied, preferring fruits and vegetables.

Ask for advice about pregnancy risks at your job.

If in doubt, consult your doctor or specialist provider.

Dioxin is a toxic substance with strong immunosuppressant, mutagenic, carcinogenic and embryotoxic effects. There is a risk of infection even when carrying out ordinary household processes - boiling tap water, washing clothes and eating fatty meat dishes.

When the poison enters the human body with water, food or air, it causes serious disturbances in metabolic processes, cell division, and the functioning of the immune and endocrine systems. It stimulates the development of malignant tumors, has a detrimental effect on the reproductive system in men and women, affects embryos and causes deformities and underdevelopment of newborns.

What is dioxin?

Dioxins are a group of complex compounds belonging to chloride derivatives of organic chemistry. It is an ecotoxicant – a substance formed exclusively as a result of human activity and unnatural for the environment. It belongs to the group of xenobiotics and is a synthetic cumulative poison - it accumulates in the fat cells of the body and is excreted very slowly. Half-life is from 7 to 11 years.

The accumulation of poison in the body has an extremely negative effect on health and leads to severe diseases - cancer, embryo mutations, chloracne, liver damage, and “chemical AIDS.”

The dose of poison that causes death is thousands of times less than the lethal dose of some toxic substances used in combat conditions - for example, sarin, soman, tabun.

Formation and mechanism of toxic action

Dioxins are released as a result of the interaction of chloride compounds with organic compounds at high temperatures. Most often, this happens in industry - poisons appear in waste and wastewater from enterprises in the metallurgical, pulp and paper, and chemical industries.

A well-known example of a global release of dioxins was the man-made disaster in 1976 in the Italian city of Seveso, at one of whose chemical plants a cloud of poison was released into the environment. As a result, for many years after the disaster, children with diseases and mutations were born in nearby cities, and the number of pathologies and mortality increased significantly.

Chlorophenol pesticides are often used to treat plants against pests and also for defoliation. If a forest treated with such herbicides catches fire, the concentration of dioxins in the atmosphere will increase significantly. An example is the defoliation of forests during the Vietnam War, when an entire generation of Vietnamese suffered after the use of a synthetic mixture of Agent Orange.

In addition, there are still many illegal landfills around the world. When man-made waste is burned, large amounts of toxic substances are released into the air.

Do dioxins form when water boils?

When pure natural water is boiled, the amount of toxic substances formed is negligible. It is much higher when using tap water, the chlorine content of which is quite high. The formation of dioxins when boiling it leads to poor health, weakness, and decreased immunity.

Routes of entry into the body

Dioxin enters the human body through air, water and food, with virtually no barriers. When carrying a child, it passes through the placental fluid. A significant excess of the level of a dangerous compound is found in the air of cities and towns surrounding industrial enterprises and located on major highways. The best environment for the sedimentation of this substance is fat cells.

The most common food sources of the toxin are:

• fatty meat (pork, lamb, etc.);
• chicken eggs;
• fatty fish (herring, catfish, etc.);
• milk and dairy products;
• leafy plants.

In addition, when washing, chlorine-containing products come into contact with organic compounds on clothing, resulting in the formation of poisons.

The substance has no smell or taste, it is transparent, so it is very difficult to understand that poisoning has occurred.

Signs of intoxication

In everyday life, in the absence of man-made disasters, dioxins accumulate in the human body for many years. In case of poisoning with them, which is chronic in nature, the following are observed:

• The appearance of chloracne - specific inflammation of the skin.
• Disruption of the endocrine and nervous systems.
• Damage to tissues and membranes of internal organs.

With a significant amount of a toxic substance, symptoms of acute intoxication appear:

• During the first 2-4 days - weakness, dizziness and mild nausea.
• Redness and itching of the skin, massive scarring, chloracne, age spots on the eyelids and behind the ears.
• Constant headache, blurred vision.
• Decreased appetite and, as a result, loss of up to a third of body weight.
• Severe irritability, drowsiness.
• Cough, shortness of breath, sputum production.
• Slowing down the regenerative processes of the skin: the wounds that appear on the skin practically do not heal.
• Severe swelling of the face.

If we consider each of the symptoms separately, it is easy to confuse dioxin poisoning with other diseases. To establish the correct clinical picture, it is necessary to pay attention to all the signs together.

Medical assistance for poisoning

Important! There is no specific antidote to dioxins.

One of the features of dioxin poisoning is that the symptoms are not unique. At home, it is difficult to determine that these substances are the cause of poor health. Therefore, first of all, it is necessary to immediately take the victim to the hospital for tests.

Consequences of dioxin exposure on the body

The toxic substance not only independently interferes with the normal functioning of cells, damaging their enzymes, but also enhances the effect of other toxins - nitrates, chlorophenols, and mercury. The body becomes more susceptible to the effects of ionizing radiation.

The main consequences of intoxication:

1. Decreased immunity due to impaired cell division, up to “chemical AIDS”.
2. Development of malignant tumors.
3. Malfunctions of the endocrine system, metabolic disorders.
4. Increased risk of infertility or the appearance of children with serious developmental problems and even mutations.

Prevention of poisoning

The appearance of dioxins is associated with widespread environmental pollution. Particularly dangerous are mass burnings of plastics and water pollution from industrial waste. It is impossible to avoid contact with poisons, but you can reduce the risk of them entering the body.

Preventive measures:

1. It is advisable to choose products of plant and animal origin from the assortment of farm enterprises located in ecologically clean areas.
2. Refuse to purchase imported food products due to the large amount of nitrates and preservatives.
3. Reduce consumption of fatty foods (pork, herring, etc.).
4. Do not use chlorinated water for drinking at home.
5. Avoid choosing a place of residence near plants or factories, as well as near household waste sites.