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Резюме Резюме Summary Рецензент: д.біол.н., проф. В.М. Кравченко УДК 615.076.9:57.017.73:582.739:633.31 Національний фармацевтичний університет (Харків) Национальный фармацевтический университет (Харьков) National University of Pharmacy Introduction. Tha fact is undeniable that the stressful situations to the body, including acute (hepatitis, poisoning, myocardial infarction) and chronic (autoimmune, renal failure, cirrhosis) diseases of internal organs and systems of various etiologies lead to hypoproteinemia, and as a result - to functional and organic violations. Scientists have calculated that the rate of protein resources of the human body without replenishing can last for 3-4 days, but during the stress – only for a few hours. Skeletal muscle proteins and some proteins of visceral organs during the stress are being exposed with the destruction and a subsequent use in other organs. Thus, after a surgery about 1,5 pounds of muscle or more than 300 grams of protein decompose within 4 days [5, 7]. In order to restore the protein balance during such states there is a need in adequate intakes of external structural components such as amino acids and other biologically active agents, correctors of the protein metabolism. In our opinion, some leguminous plants (Fabaceae), Lucerne crop (Medicago sativa) and soybean bristly (Glycin hispida Maxim) can be the source of these substances. Owing to this fact, the scientists of the National University Of Pharmacy have received the Medicago sativa sowing grass (EGMS) and Glycine hispida sowing grass (EGGH) and found the content of biologically active substances. [3, 9]. The presence in the contents of EGMS and EGGH large amounts of proteins, amino acids, including essential enzymes, vitamins, micro- and macroelements contribute to the correction of protein metabolism in the body and thus restore its plastic, structural, energy and other functions. By stimulating the synthesis of endogenous sex hormones, which are known to stimulate the biosynthesis of proteins, phytoestrogens and isoflavones will correct the protein metabolism. Flavonoids, organic acids, tannins, which are characterized with the presence of antioxidant, anti-inflammatory, membrane and organprotective substances will help to restore the functional activity of vital organs, including the liver, which takes proteinsynthetic function, and thus also helps to restore the level of protein in the body. The Glycine hispida sowing grass contains phenolic compounds including flavonoids, isoflavones, tannins, organic acids, benzoic acids, polysaccharides, pectins, free and bound amino acids [9]. Considering the ideas mentioned above, the aim of this study was to determine the effective dose of EGMS in comparison with EGGH and potassium orotate with the effect on protein metabolism in healthy mature rats as a potential protein metabolism corrector. Materails And Methods That study of the influence of the EGMS and EGGH in comparison with a reference drug of potassium orotate on the protein metabolism in the body have been performed using 48 mature white rats, out of which there were formed 6 groups of 8 animals in each: the first group – intact control (IC), the second group – animals treated with "Potassium orotate" (PO) at a dose of 180 mg/kg, the third group – animals that received the EGMS at a dose of 25 mg/kg, the fourth group – animals that received the EGMS at a dose of 50 mg/kg, the fifth group – animals that received the EGMS at a dose of 100 mg/kg and the sixth group – animals that received the EGGH at a dose of 100 mg/kg. The animals have been kept on a standard diet vivarium CSRL of the NUPh in accordance with the established standards [2, 6]. The research has been conducted in the compliance with the humane treatment of animals in accordance with the rules of the "European Convention for the protection of vertebrate animals used in the experiments and other scientific purposes" (Strazburh, 1986) [2]. As a reference drug we have selected the "Potassium Orotate" producted by PJSC SIC "Borshchahivskiy CPP" (Kyiv), which is the only one non-steroidal drug allowed in Ukraine that is used in the clinic for the violations in the protein metabolism and as a general stimulant of the metabolism. The dose of potassium orotate – 180 mg/kg – have been defined in terms of the process of the daily human dose (according to the instructions the maximum daily dose can be used for adults is 3000 mg) against a daily dose for the rat according to the method by Rybolovleva Yu.P. [8]. To study the effect of these substances on the state of the protein metabolism they have been intragastrically administered at doses described above, within 28 days. After the experiment, all animals have been weighed, anesthetized with the thiopental sodium (50 mg/kg) and deduced from the experiment with the decapitation. Next, we have determined the mass and the mass coefficient (MC) of the gastrocnemius muscle, liver and heart [4]. The results have been processed statistically using the parametric and nonparametric methods with the help of the program Statistica 6. The ability to adjust the protein metabolism have been evaluated by the change in a body weight and viscera and MC in the animal of the researching groups compared with the intact control [1]. Results And Their Discussions Analysis of the influence of EGMS, EGGH and reference drug of potassium orotate on the protein metabolism indicates that all the study material have contributed to increase the weight of the experimental animals compared with the intact ones which indicates their ability to the correction of protein metabolism. Thus the increase of the weight of the mature animals compared with the intact control under the influence of the comparison drug " Potassium Orotate " was 12,5 %, EGMS at a dose of 25 mg / kg – 46,88 % , EGMS at a dose of 50 mg/kg – 28,13 %, EGMS at a dose of 100 mg / kg – 17,2 %, EGGH – 9,38 %, but reliable one when compared with the intact control group was an absolute increase of the weight only in the group of the animals, which were administered with the EGMS at a dose of 25 mg/kg, which was almost 59 g. The comparative analysis of the dynamics of the body weight of the animals has showed that according to the ability to stimulate the growth of the mass the plant extracts prevail or are at the same level with the comparison drug "Potassium Orotate" (Table 1). So in terms of "Increase of the body weight relative to IC" the EGMS at a dose of 25 mg/kg prevailed the rates in the group that received a "potassium orotate" by 3,75 times, EGMS at a dose of 50 mg/kg – by 2,25 times, in EGMS at a dose of 100 mg/kg – by 1,4 times, and the increase of the body weight relative to IC influenced by EGGH at a dose of 100 mg/kg has been at the same level as the comparison drug. The results of the determination of the mass and mass coefficient of the gastrocnemius muscle, liver and heart that are more intensive than the other agencies involved in the protein metabolism, indicate that the studied substances help to increase the weight of the gastrocnemius muscle and liver and do not affect the weight of the heart. Thus, the mass and the mass coefficient of the gastrocnemius muscle are increased compared with the intact control group under the influence of the comparison drug " Potassium Orotate " by 1,2 times, EGMS at a dose of 25 mg/kg – by 1,3 times, EGMS 50 mg/kg – by 1,1 times, EGMS at a dose of 100 mg/kg – by1,14 times, EGGH – by 1,13 times. The changes of mass and mass coefficient of the gastrocnemius muscle, reliable according to the IC group, have been observed only under the action of EGMS at a dose of 25 mg/kg and their value is dominated by the same results of the comparison drug "Potassium Orotate" by 11 %. There has been indicated the increase of the mass and the mass coefficient of the liver under the influence of the reference drug "Potassium Orotate" by 15%, EGMS at a dose of 25 mg/kg – by14%, EGMS at a dose of 50 mg/kg – by 3%, EGMS at a dose of 100 mg/kg – by 3%, EGGH – by 3% (Picture 2). Reliably according to the IC group and at the same level there has been the increase of the mass and the mass coefficient of the liver under the influence of "Potassium Orotate" and EGMS at a dose of 25 mg/kg. Conclusions It has been established that EGMS at a dose of 25 mg/kg has showed the most expressive regulatory effect on the protein metabolism compared with the doses of 50 mg/kg and 100 mg/kg. It has been established that EGMS at a dose of 25 mg/kg and EGGH at a dose of 100 mg/kg have the ability to correct the protein metabolism by inducing the synthesis of proteins in organs and tissues. The comparative analysis of the results has helped to conclude that the Medicago sativa sowing grass at a dose of 25 mg/kg, according to the ability to induce the accumulation of proteins in the body prevails the comparator "Potassium Orotate" at a dose of 180 mg/kg by 1,1-3,75 times, and is promising for the further research and creation of a new drug, corrector of the protein metabolism, on its basis. Література
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