The method of prevention and treatment of atherosclerosis in the experiment

 

(57) Abstract:

The invention relates to medicine, in particular to the experimental therapy, and for the prevention and treatment of atherosclerosis. The method is intramuscular in the body of the animal uridine at a dose of 50 mg per 1 kg of body weight once a day during 6-8 days. The method has an impact on all pathogenic components of the disease. table 1.

The invention relates to medicine, namely to methods for treatment and prevention of atherosclerosis.

All the numerous means of prevention and treatment of atherosclerosis is aimed at lowering lipids in the blood and tissues.

The mechanism of action, they are divided into the following groups.

1. Drugs, mainly to reduce cholesterol in the blood (this Department N. A. lipid-lowering means. Cardiology, N 3, 1994, S. 49-69; Thomson, R. (London). Guide hyperlipidemia. 1991, S. 193-213).

a). Anion-exchange resin or the biliary acids (cholestyramine, colestipol). They bind bile acids in the intestine and increase their excretion. It stimulates the transfer of cholesterol from the blood to the liver for synthesis of new portions of bile acids.

b). Statins - drugs that inhibit the synthesis of cholesterol in the liver by inhibiting the enzyme MMC-COA reductase, which controls one of the stages of this synthesis (lovastatin, mevastatin, simvastatin). The most widespread use of this group of drugs received lovastatin, which is used in a dose of 20-80 mg. But frequent side effect when using it is myopathy, which is not always an opportunity to use it for a long time, which is necessary to obtain anti-sclerotic effect.

in). Neomycin - prevents the absorption of cholesterol in the intestine by forming with them insoluble complexes, however, necessary for the treatment dose (0.5-1.0 g per day) is toxic, causes ear infections and diarrhea.

2. Drugs, mainly reducing the level of triglycerides in the blood (this Department N. A. lipid-lowering means. Cardiology, N 3, 1994, S. 49-69; Thomson, R. (London). Guide hyperlipidemia. 1991, S. 193-213).

a). Nicotinic acid. Its lipid-lowering effect due to the lowering of education VLDL in the liver, the main component of the cat(1.5 to 3 g per day), when it has a negative effect on the liver, exacerbates chronic diseases of the gastrointestinal tract, increases the frequency of cardiac arrhythmias causing sudden reddening of the skin, hyperglycemia, and hyperuricemia.

b). Fibrates (clofibrate, benzafibrate, gemfibrozil, ciprofibrate, fenofibrate). Increase the catabolism of VLDL, without changing the speed of their synthesis, and increase the excretion of bile acids.

Drugs in this group, especially clofibrate, have a number of significant side effects: the formation of gallstones, myopathy, gastrointestinal disorders and a number of others. The most common of this group of medicines is gemfibrozil used in a dose of 900-1200 mg / day.

3. Recently, great attention to attract funds, the main active component of which are long chain polyunsaturated fatty acid (concentrate fish oil-Maxepa, Essentiale) (this Department N.R. Lipid-lowering means. Cardiology, No. 3, 1994, S. 49-69; Thomson, R. (London). Guide hyperlipidemia. 1991, S. 193-213).

These tools reduce the rate of synthesis of triglycerides, promote the synthesis of phospholipids, normalize energy obmana at high doses, the consequences of which are poorly understood. There is a proposal to autookislenia polyunsaturated fatty acids in the body, which can contribute not regression, and the development of atherosclerosis.

4. The new hypolipidemic drug used for the treatment of atherosclerosis, is also probucol, mechanism of action which is associated not only with its lipid-lowering properties, but also with antioxidant activity, which reduces peroxidation of LDL in macrophages-monocytes and related their transformation into foam cells of atherosclerotic plaques. However, clinical trials of this drug only deployed, and yet not enough is known about its side effects. There are indications of the possibility of the action of ventricular tachycardia and disorders of the gastrointestinal tract (this Department N. A. lipid-lowering means. Cardiology, N 3, 1994, S. 49-69; Thomson, R. (London). Guide hyperlipidemia. 1991, S. 193-213).

As a prototype adopted a method of treating atherosclerosis by introducing into the body of clofibrate. However, this drug causes serious side effects: obrazovanju) 3 R. in day. Treatment for a long time - courses for 20-30 days with the same intervals (4-6 courses) (Thomson, R. Guide hyperlipidemia. 1991, S. 193-213).

The objective of the invention is to provide a highly efficient method for the prevention and treatment of atherosclerosis, and to prevent the progression of the disease.

The invention is a method for prevention and treatment of atherosclerosis, including the introduction of medicinal substances, intramuscularly, uridine at a dose of 50 mg per 1 kg of body weight once a day during 6-8 days of treatment.

The use of the invention allows to obtain the following technical result.

The method is highly efficient, because the impact is on all pathogenic components of the disease.

The treatment time in comparison with all known methods are drastically reduced and are only 6-8 days of treatment.

The method allows to regulate carbohydrate metabolism.

Reduces symptoms of clinical symptoms.

The method can be successfully used both for prevention and treatment of atherosclerosis.

The technical result is achieved with the o the uridine reduces the incidence and severity of atherosclerotic lesions in the aortic wall. His anti-sclerotic effect is linked to the ability to stimulate the conversion of fatty acids into carbohydrates. This leads to the reduction of lipid deposits in an intim of the aorta and cardiac muscle, as well as increased glycolytic energy supply of tissues. In addition, under the influence of uridine reduced content of calcium in the blood, which prevents damage of the vascular endothelium (see table).

The method is as follows: in the body daily for 6-8 days is administered by intramuscular injection, an aqueous solution of uridine at a dose of 50 mg/kg of body weight.

The method was pilot-tested in the Department of experimental and clinical medicine science RMAPO.

Experimental studies were carried out on outbred rats-males weighing 250-300 g Modeling of atherosclerosis was carried out according to the method of Altman (1973). In accordance with cholesterol (1-% oil solution) was administered orally through a feeding tube in a dose of 40 mg/kg body weight. After 1 hour, then the same method was introduced drugstore oil solution of vitamin D2dose 350000 IU/kg of body weight.

The uridine (firm Reanal - Hungary) was administered intramuscularly at a dose of 50 mg/kg of body weight once a day a few hours after administration of vitamin D2.

Thus, in the first two days of the experiment, rats were treated with cholesterol and vitamin D2and in the following days - cholesterol, vitamin D2and uridine. On the 9th day from the beginning of the experiment (on the 7th day of the introduction of uridine) under Nembutal anesthesia in rats took blood for biochemical studies and after decapitate - samples of liver, heart and thoracic aorta for morphological studies (light and electron microscopy, cytochemistry, morphometry).

All biochemical data were subjected to statistical analysis. Differences were significant for glucose, lactic acid and calcium.

The work is performed on 20 animals (10 - without treatment of atherosclerosis and 10 - treatment uridine).

The increase in the level of hyperglycemia, we explain the increased glycolytic processes in tissues (liver, cardiac muscle, aorta) under the action of uridine. This is due to the fact that the uridine is not only the nucleotide and coenzyme glycogen synthase (glycogen - UDF - glucosyl. the. Cytology, 1985, I. XX II, S. 157-160., Bull. the experts. Biol, and med. 1987, 12, S. 734-736 and others).

All the essence of the treatment of atherosclerosis by uridine is that it puts the excess coming in liver, heart and aorta fatty acids into carbohydrates and thereby prevents the accumulation of fat and cholesterol. In addition, as a nucleotide, it contributes to reduction processes in the damaged cells.

There are some literature data (Elisha C. C. et al. Chem. Pharm.W. 1989, 3, 27, S. 273) favorable effect of uridine in experimental myocardial infarction associated with increased activity of enzymes of glycolysis and glycogen resynthesis. However, the positive effect of uridine with atherosclerosis and its mechanism of action is through the transformation of fat into glycogen shown for the first time.

The authors are confident in the prospect of the creation of dosage forms on the basis of uridine for the prevention and treatment of atherosclerosis.

Certainly, short term use of uridine in rats to humans will be longer when comparing life expectancy, weight and other conditions, and the development of therapeutic drugs is a separate issue which will help the experimental results.


 

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9 cl, 1 tbl, 8 ex

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