CC BY
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Section 4. Medical science
Kasimova Gulnorakhon Zulfikarovna, The assistent of Andijan State Medical Institute
Sabirova Rikhi Ablukadirovna, The professor of Tashkent Medical Academy E-mail: evovision@bk.ru
Influence of various forms chitosan on microsomal oxidation in the liver and metabolic syndrome
Abstract: Chitosan derivatives, to a greater extent chitosan nano, positive impact on the recovery of impaired activity of microsomal enzyme systems that can be considered to be one of the reasons for reduction factors for MS in experimental animals. Keywords: metabolic syndrome, liver, microsomale and mithochondrial oxidation, hitozan.
The clinical significance of metabolic syndrome (MS), the combined framework syndrome is the presence of a whole range of risk factors, which are formed long before its development. An important place in this case takes the liver [1]. In clinical practice, the connection MS with impaired liver function is defined as the term "diabetic steatosis» (Canadian Diabetes Association, 2003). Despite the importance of the liver disorders in the development of MS many aspects of pathogenesis of this disease with hepatocytes, in particular molecular-cellular mechanisms remain unclear. Especially there is no clear clarity of microsomal oxidation in the liver with the formation of MS.
Ofparticular interest is the study of the effect on the liver microsomal oxidation membrane protectors. There is some evidence that chitosan and its isoforms may positively affect the functional activity of the liver in acute and chronic hepatitis [2]. However, it remains unclear how does chitosan and its isoforms at the subcellular level in the liver with the formation of MS.
The aim of this study was to investigate the microsomal oxidation in the liver and the impact of various forms of chitosan on these processes.
Material and methods. Experiments were carried out on 60 male rabbits, weighing from 2050 to 3400. The metabolic syndrome in rabbits is caused by the method S. A. Saidov [3]. To create a model of metabolic syndrome in animals trough added 5 % sugar solution and mixed in a daily feed crystalline cholesterol of 250 mg/kg body weight. Animals were subcutaneously injected insulin dose of 0.1 units./100 g., a day. The duration of 2 months. Animals were divided into 5 groups: Group 1 (intact) contained in natural vivarium conditions (12 rabbits); 2 group — caused metabolic syndrome (12 rabbits); Group 3 — correction of metabolic syndrome chitosan sulfate (12 rabbits); Group 4 — correction of metabolic syndrome with nana form of chitosan sulfate (12 rabbits); Group 5 — the comparison group, where the correction of the metabolic syndrome was performed with glucophage. Chitosan is a deacetylation product of chitin. The chemical structure of chitosan is a sopolymer of D-glucosamine and N-acetyl -D-glucosamine. Chitosan is a universal sorbent capable of binding a huge range of substances of organic and inorganic nature, which defines the broadest possible application in human life. The study examined the effect of chitosan sulfate and Nana form synthesized based on chitosan Bombyx mori, represented by the Institute of Physics and Chemistry of the Academy of Sciences of Uzbekistan (Head of Laboratory, c. c. s. Dr. R. Y. Milusheva).
For correction MS used sulphate chitosan Chitosan obtained sulfation reaction medium in chlorosulfonic acid. Orally aqueous solution of chitosan and its sulfate nano form administered 25 mg/kg over 20 days after receiving a model of metabolic
syndrome. Glucophage, according to the instructions of the drug was administered orally at the rate of — 7.14 mg/kg body weight.
Isolation of liver microsomal fractions was performed by differential centrifugation on a refrigerated centrifuge RL-6 and VAC-601. The contents of cytochrome P-450 in the microsomal suspension was determined with a spectrophotometer UV/VIS (LTD, China) by the method of Omura T., Sato R. [4]. The content of cytochrome b5 were determined after recovery experienced microsomal suspension samples by the addition of NADH. Activity amidopyrine demethylase-N-method Bast A., Nordhoock J. [5] anilingidroksila-zy — by A. I. Archakov et al. [6], NADPH-cytochrome C reductase (NADPH cyt. P-ed) by the method Willians C. H., Kamin H. [7] and microsomal protein of O. N. Lowry [8].
Results and discussion
Studies have shown that after 2 months from the beginning of the simulation of the experimental MS in liver microsomes of cytochrome P450 and b5 was significantly reduced by 28.6 (P < 0.01) and 17.2 % (P < 0.05), respectively, compared with the intact group (Table 1). Activity-NADPH-cytochrome c reductase, amino-pyrine demethylase-N-, anilingidroksilazy animals of this group decreased 2.48; 1.93 and 2.14 times, respectively, compared to the intact group. This enzyme system plays an important role in metabolizing both endogenous (steroid hormones, cholesterol, fatty acids and bile acids, prostaglandins) or exogenous (xenobi-otic majority) substrates, it is fully functional condition depends on the integrity of the endoplasmic reticulum membrane structures.
Therefore, these results indicate a marked inhibition of microsomal oxidation in liver at metabolic syndrome.
NADPH-cytochrome P450 microsomal electron transport system is in constant renewal de novo protein enzyme complexes, metabolic activity which is largely dependent on the varying conditions of physiological and pathological processes in the cells [9]. Thus protein synthesis de novo enzyme complexes requires considerable use of ATP and NADPH. Mitochondrial and microsomal system compete for connection to the NADPH in the process of using it for free in the mitochondrial respiration and with the mating operation of the cytochrome P-450 systems, the smooth endoplasmic reticulum [9].
Inhibition of the activity of the liver MOS at the metabolic syndrome may be due to a deficiency of NADPH — as the main source for the functioning of NADPN — cytochrome c reductase in microsomes, as noted in our research. Currently offers a variety of methods to restore the microsomal oxidation processes, including chitosan derivatives.
The literature suggests that the chitosan, providing sorption, lipotropic, and lipid-lowering effect and stimulating the motility of the gastrointestinal tract and biliary tract, promotes the normalization of metabolic processes.
Precancerous diseases in the structure of oral mucosa pathology
Table 1. - Effect of chitosan derivatives on microsomal oxidation in the liver of rabbits with the metabolic syndrome (M ± m)
Group Microsomes
P-450, nmol/mg b5, nmol/mg NADPN - cyt.- c. red. nmol/min/mg AN, nmolHCHO/ min/mg AG, nmolaminofen/ min/mg
Intact 0.985 t 0.030 0.593 t 0.021 94.4 t 8.48 7.0 t 0.492 1.09 t 0.06
MS 0.703 t 0.024* 0.491 t 0.004* 38.0 t 2.94* 3.6 t 0.28* 0.51 t 0.026*
MS + chito-san sulfate 0.775 t 0.033* 0.484 t 0.024* 49.6 t 3.27* 4.4 t 0.30*, ** 0.57 t 0.024*
MS+chitosan sulfate nano 0.837 t 0.026*' **' *** 0.518 t 0.019* 53.8 t 2.48*, **, *** 5.5 t 0.177*, **, *** 0.67 t 0.034*, **, ***
MS+glyuko fazh 0.706 t 0.032* 0.497 t 0.021* 45.7 t 1.76* 3.6 t 0.28* 0.54 t 0.032*
Note: * — differences with respect to the data of the control group significant: * — P < 0.05; ** — P < 0.01; *** — P < 0.001.
Investigating the effects of two forms of chitosan — chitosan sulfate and it's nano forms on monooxygenase system showed a significant increase in the content of cytochrome P-450. When administered chitosan and its sulfate form nano levels of cytochrome P-450 exceeded by 10.2 and 19.1 % (P < 0.05 and P < 0.05, respectively) compared to those animals with MS parameters. Chitosan Sulfate and its nano form of significant changes in the content of cytochrome b5 causes. Chitosan Sulfate significantly to 30.45 % (P < 0.01) increases the activity of only NADPH-cytochrome c-red. compared to the untreated group. At the same time nano form of chitosan sulfate increases more significantly as the activity of NADPH-cytochrome c-red and aminopyrine demethylase-N-,
anilingidroksilazy 41.6; 53.6; 31.7 % (P < 0.001), respectively, compared with the untreated group.
A study comparing the action of the drug — Glucophage has shown that it is not sufficiently active to enhance the functional activity of the microsomes. Glucophage is widely used as a means of correction dismetabolic disorders in MS development. Perhaps it is not related to the effect of the influence on the processes oxidase and oxygenase way of oxidation.
Conclusions
Thus, studies have shown that the development of MS is observed pronounced inhibition of the functional activity of cyto-chrome P-450 system in the liver microsomes.
References:
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6. Гидроксилирование производных анилина и аминоантипирина (1-фенил-2,3-диметил-аминопиразолон-5) в эндоплазматическом ретикулуме печени/А. И. Арчаков, И. Н. Карузин, В. Н. Тверитапов, И. С. Кокарева//Биохимия. - 1975. - Т. 40, вып. 1. - С. 29-32.
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Kolenko Yulia Gennadiivna, A. A. Bogomolets National Medical University, Kyiv, PhD, Associate Professor E-mail: kolenko.julia@gmail.com
Precancerous diseases in the structure of oral mucosa pathology
Abstract: The study presents the results of the research on the structure, local and systemic risk factors, peculiarities of the clinical manifestation, quality of primary diagnosis of precancerous oral mucosa lesions and red border of the lip. The high percentage of diagnostic errors and lack of oncological awareness of dentists, as well as the necessity of inclusion of precancer early detection techniques are noted.
Keywords: precancerous oral mucosa diseases, early diagnosis, the occurrence of diseases of oral mucosa diseases.
Many forms of oral mucosa diseases and red border of the lips According to experts [5; 8], the share of oncological diseases of
characterized by chronic relapsing course, occur with severe clini- the maxillofacial region is accounted for 2.4 % of all malignant neo-
cal symptoms, can provoke the development of systemic diseases, plasms, and "coarse" and standardized mortality rates from malig-and lead to a reduction of dental quality of life [2; 3]. Many chronic nant tumors of the maxillofacial area (lip, tongue, salivary glands,
diseases of the oral mucosa have a high oncogenic potential [4]. other and unspecified parts of the oral cavity, oropharynx) in
