Recombinant erythropoietin. Recombinant human erythropoietin

Erythropoietin (EPO) is a glycoprotein hormone that controls the rate of erythropoiesis in the human body. The substance is synthesized mainly in the kidneys, a small amount (about 10 percent) is formed in the liver. The hormone erythropoietin activates the division and differentiation of erythroid progenitors. The level of endogenous hormone in the blood plasma of healthy people varies in a wide range and is inversely related to the concentration of hemoglobin and the degree of oxygenation of tissues. The work on the isolation and production of this hormone for medicine is very useful.

Structure and significance of the hormone

The hormone molecule consists of amino acids. With a deficiency of endogenous erythropoietin, a sharp decrease in the level of hemoglobin and erythrocytes in the blood is observed, so-called erythropoietin deficiency anemia develops. Until recently, pharmacological correction of such anemia remained impossible due to the absence of an appropriate pharmaceutical agent. Today, with the deficiency of the above hormone in the human body, physicians prescribe recombinant erythropoietin. The preparation is obtained from animal cells into which the gene code of human EPO is introduced. Recombinant human erythropoietin in amino acid and carbohydrate composition is identical to natural hormone, increases the number of red blood cells, reticulocytes, activates the biosynthesis of hemoglobin in cells. The biological activity of the obtained substance is no different from the endogenous hormone. Recombinant erythropoietin does not exhibit a cytotoxic effect and does not affect leukopoiesis. Scientists suggest that the EPO interacts with specific erythropoietin-sensitive receptors that are localized on the surface of the cell.

A method for purifying recombinant human erythropoietin

Recombinant human EPO is one of the most common proteins produced by many biological and pharmaceutical companies around the world for drug therapy. The present compound is synthesized by Chinese hamster ovary (CHO) cells by the recombinant DNA method. One polypeptide chain of recombinant EPO contains 165 amino acids with a calculated molecular weight of 24,000 Da, and the observed molecular weight of the glycosylated protein is 30,400 Da. The separation of erythropoietin from impurities is carried out by ion exchange and affinity chromatography. The human recombinant EPO has a purity of 98%.

Recombinant erythropoietins and their analogues

To stimulate the processes of erythropoiesis, medics use different drugs:

• "Aranesp";
• "Aeprin";
• "Epobiocrine";
• Bioin;
• Vepox;
• Binocrit;
• "Epokrin";
• "Gemax";
• "Epogen";
• "Eprex";
• "Epovitan";
• "Epomax";
• Hyperkrit;
• "Eralfon";
• "Erythrostim";
• "Recormon";
• "Eposimus";
• "Eposino";
• "Epoetin Beta".

Before replacing recombinant erythropoietin with analogs, one should consult a doctor in charge.

Indications for use

Practitioners often have to deal with erythropoietin deficiency anemia (EDA). This group includes the following pathologies:

• Anemia in malignant neoplasms;
• Early anemia of premature babies (before 34 weeks gestation) with body weight from 750 to 1500 g;
• Nephrogenic anemia;
• Anemia in chronic diseases (hepatitis C, rheumatoid arthritis, HIV infection, diseases of the digestive canal).

A distinctive feature of the above anemia is that they are not treated with iron preparations. Until recently, the only effective method of therapy were blood transfusion. In connection with the fact that this type of therapy has a huge number of side effects and a high risk of blood transfusion pathogens of a number of dangerous infectious diseases (HIV, hepatitis viruses, etc.), this method is not used in modern medicine. Recombinant human erythropoietin helps improve the quality of life for patients diagnosed with erythropoietin deficiency anemia. Biosynthesis and the introduction into practice of recombinant human EPO have opened a new era in the treatment of erythropoietin-dependent anemias.

Contraindications

Doctors do not recommend the use of recombinant erythropoietin (the instruction warns about it) in the presence of the following pathologies:

• Thromboembolism;
• Hypersensitivity to the drug;
• Impossibility of effective anticoagulant therapy;
• A stroke of the brain or myocardial infarction;
• Unstable angina;
• Uncontrolled arterial hypertension;
• The period of bearing and breastfeeding;
• Refractory arterial hypertension.

Dosing regimen

Dosage, schedule and duration of treatment are established in strictly individual order, depend on the severity of anemia, the general condition of the patient and the nature of the pathology. Preparations are intended for parenteral use. Initial doses range from 50 to 150 IU / kg. The dose needs to be adjusted depending on the age of the patient. Recombinant erythropoietin, as a rule, is administered 3 times a week. When an overdose of the drug, there is an increase in side effects. The result becomes more or less noticeable after only 2-3 weeks of use.

Side effect

Are recombinant human erythropoietin assigned to you? Instructions for use do not preclude the development of side effects. It:

• Myalgia;
• dizziness;
• Hyperthermia;
• drowsiness;
• Vomiting;
• headache;
• diarrhea;
• arthralgia;
• hypertension;
• Pain in the chest;
• Thrombocytosis;
• tachycardia;
• hypertensive crisis;
• Convulsions;
• Hepatosis;
• Increase in the level of activity of AST, ALT in the blood;
• Aplasia of erythrocyte sprout;
• eczema;
• Angioedema;
• Skin rash and itching;
• asthenia;
• Urticaria, flushing and burning at the injection site;
• Hyperkalemia;
• Decrease in the concentration of the ferritin protein in blood plasma;
• Hyperphosphataemia.

Stimulants of erythropoiesis in sports

Recently, the drug "Epovitan" (recombinant human erythropoietin) is often used. The presented tool is often used in sports (athletics, bodybuilding, swimming, biathlon). This drug activates the biosynthesis of erythrocytes, which in turn leads to an increase in the oxygen content per unit volume of blood and, accordingly, to an increase in the oxygen capacity of the blood and the delivery of O ₂ to organs and tissues. This mechanism of action increases the athlete's aerobic endurance. A similar effect is observed in the athlete's training in mid-mountain conditions, when the lack of O ₂ in the air provokes the development of hypoxia, which, in turn, activates the biosynthesis of endogenous erythropoietin. EPO preparations are used in combination with insulin, somatotropin (STH, somatotropic hormone) and stanazolol.

Excessive, uncontrolled use of the drug "Erythropoietin" in sports can provoke the formation of thrombi, which usually leads to death. It is quite difficult to detect recombinant EPO, since the structure of the synthetic compound is identical to its physiological analogue, therefore this bio-compound is still illegally used in large sports as doping.