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217ОМЕГА-3 И БИОХИМИЧЕСКИЕ ПРОЦЕССЫ ВОСПАЛЕНИЯ В ОРГАНИЗМЕ
Эргашева Зумрад Юлдашева Гульнора Абдурахимов Абдухалим Нугманов Озодбек
Андижанский государственный медицинский институт
Андижан, Узбекистан
Омега-3 это группа ненасыщенных жирных кислот, в большом количестве содержащихся в рыбьем жире и семенах льна. Они обладают многими полезными свойствами для организма. В частности, отмечено их влияние в улучшении деятельности мозга, сердечно-сосудистой системы, желудочно-кишечного тракта. В литературных источниках также имеются данные, что они укрепляет иммунную систему организма, снижают уровень холестерина и оказывают эффективное противовоспалительное действие. В данной статье обсуждаются особенности течения биохимических процессов при воспалении, а также влияние омега-3 жирных кислот на эти процессы.
Ключевые слова: омега-3, холестерин, биохимия воспаления.
OMEGA-3 VA ORGANIZMDAGI YALLIG'LANISHNING BIOKIMYOVIY
JARAYONLARI
Omega-3 foydali yog' kislotalari hisoblanib, baliq yog'i va zig'ir o'simligining urug'ida ko'p miqdorda uchraydi. Uning organizm uchun foydali xususiyatlari juda ko'p. Xususan, bosh miya faoliyati, yurak-qon tomir tizimi, oshqozon-ichaklar faoliyatini yaxshilaydi. Bundan tashqari organizda immunitet tizimini kuchaytiradi, xolesterin miqdorini kamaytiradi va yallig'lanishga qarshi samarali ta'sir ko'rsatishi fanga ma'lum. Ushbu maqolada yallig'lanishdagi biokimyoviy jarayonlar hamda omega-3 ning ushbu jarayonlarga ta'siri haqida so'z bormoqda.
Kalit so'zlar: Omega-3, xolesterin, yallig'lanishning biokimyosi.
OMEGA-3 AND BIOCHEMICAL PROCESSES OF INFLAMMATION IN THE BODY
Omega-3 is a beneficial oil found in fish oil and flaxseed seeds. It has many useful properties for the body. In particular, it improves the activity of the brain, cardiovascular system, gastrointestinal tract. It is also known to science that it strengthens the immune system in the body, lowers cholesterol and has an effective anti-inflammatory effect. This article discusses the biochemical processes in inflammation as well as the effects of omega-3 on these processes.
Keywords: Omega-3, cholesterol, biochemistry of inflammation.
DOI: 10.24411/2181-0443/2020-10075
Introduction: Studies show that [1] what eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are able to inhibit partly a number of aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leuœtrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines and T cell reactivity. In
parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonioc acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving resolvins and protectins. Mechanisms underlying the antiinflammatory actions of n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor NR1C3 (i.e. peroxisome proliferators activated receptor g) and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked. In adult humans, an EPA plus DHA intake greater than 2 g day-1 seems to be required to elicit anti-inflammatory actions, but few dose finding studies have been performed. Animal models demonstrate benefit from n-3 fatty acids in rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in patients with RA demonstrate benefit supported by meta-analyses of the data. Clinical trails of fish oil in patients with IBD and asthma are inconsistent with no overall clear evidence of efficacy.
It became known to science [2, 3] what Omega-3 (n-3) polyunsaturated fatty acids: a brief overview The term omega-3 (w-3 or n-3) is a structural descriptor for a family of polyunsaturated fatty acids (PUFAs). n-3 signifies the position of the double bond that is closest to the methyl terminus of the acyl chain of the fatty acid. All n-3 fatty acids have this double bond on carbon 3, counting the methyl carbon as carbon one. Like other fatty acids, n-3 fatty acids have systematic and common names, but they are frequently referred to by a shorthand nomenclature that denotes the number of carbon atoms in the chain, the number of double bonds, and the position of the first double bond relative to the methyl carbon. The simplest n-3 fatty acid is a-linolenic acid (18:3n-3). a-linolenic acid is synthesized from the n-6 fatty acid linoleic acid (18:2n-6) by desaturation, catalyzed by delta-15 desaturase. Animals, including humans, do not possess the delta-15 desaturase enzyme and so cannot synthesize a-linolenic acid. In contrast, plants possess delta-15 desaturase and so are able to synthesize a-linolenic acid. Although animals cannot synthesize a-linolenic acid, they can metabolize it by further desaturation and elongation. Desaturation occurs at carbon atoms below carbon number 9 (counting from the carboxyl carbon) and mainly occurs in the liver. A-linolenic acid can be converted to stearidonic acid (18:4n-3) by delta-6 desaturase and then stearidonic acid can be elongated to eicosatetraenoic acid (20:4n-3), which can be further desaturated by delta-5 desaturase to yield eicosapentaenoic acid (20:5n-3; known as EPA). It is important to note that the conversion of a-linolenic acid to EPA is in competition with the conversion of linoleic acid to arachidonic acid (20:4n-6) since the same enzymes are used. The delta-6 desaturase reaction is rate limiting in this pathway. The preferred substrate for delta-6 desaturase is a-linolenic acid. However, linoleic acid is much more prevalent in most human diets than a-linolenic acid, and so metabolism of n-6 fatty acids is quantitatively the more important. The activities of delta-6 and delta-5 desaturases are regulated by nutritional status, hormones and by feedback inhibition by end products. The pathway for conversion of EPA to docosahexaenoic acid (22:6n-3; known as DHA) involves addition of two carbons to EPA to form docosapentaenoic acid (22:5n-3; known as DPA), addition of two further carbons to produce 24:5n-3, desaturation at the delta-6 position to form 24:6n-3, translocation of 24:6n-3 from the endoplasmic reticulum to peroxisomes where two carbons are removed by limited b-oxidation to yield DHA (summarized in Figure 1). Short term studies with isotopicallylabelled a-linolenic acid and long term studies using significantly increased intakes of a-linolenic acid have demonstrated that the conversion to EPA, DPA and DHA is generally poor in humans, with very limited conversion all the way to DHA being observed. EPA, DPA and DHA are found in significant quantities in fish (see below), and so in this article these three fatty acids are collectively referred to as marine n-3 PUFAs. Because a-
linolenic acid is produced in plants, green leaves and some plant oils, nuts and seeds contain moderate to high amounts of it and usually a-linolenic acid is the major n-3 fatty acid consumed in most human diets [4]. However, the main PUFA in most Western diets is the n-6 linoleic acid which is typically consumed in 5 to 20-fold greater amounts than a-linolenic acid [4]. Seafoods are a good source of marine n-3 PUFAs [4]. These fatty acids are found in the flesh of both lean and oily fish, with much greater amounts in the latter, and in the livers of some lean fish (e.g.cod).In people who eat little fish,intakes of marine n-3 PUFAs are low (typically < 0.2 g dayand probably much lower than this [5]). A single lean fish meal (e.g. one serving of cod) could provide about 0.2 to 0.3 g of marine n-3 fatty acids,while a single oily fish meal (e.g. one serving of salmon or mackerel) could provide 1.5 to 3.0 g of these fatty acids. Fish oil is prepared from the flesh of oily fish (e.g. tuna) or from the livers of lean fish (e.g. cod liver). In a typical fish oil supplement EPA and DHA together comprise about 30% of the fatty acids present, so that a 1 g fish oil capsule will provide about 0.3 g of EPA + DHA.However, the amount of n-3 fatty acids can vary between fish oils, as can the relative proportions of the individual marine n-3 PUFAs. Encapsulated oil preparations that contain n-3 fatty acids in higher amounts than found in standard fish oils are available ('fish oil concentrates'). In fish oil capsules the fatty acids are usually present in the form of triacylglycerols.However,marine n-3 fatty acids are also available in the phospholipid form (e.g.in krill oil) and as ethyl esters (e.g.in the highly concentrated pharmaceutical preparation Omacor (Pronova Biocare, Lysaker, Norway), known as Lovaza (GlaxoSmithKline, St Petersberg, FL, USA) in North America).
According to Bagga D, Wang L, Farias-Eisner R, Glaspy J. A, Reddy S. T [6] Omega-6 (omega -6) polyunsaturated fatty acids (PUFA), abundant in the Western diet, are precursors for a number of key mediators of inflammation including the 2-series of prostaglandins (PG). PGE2, a cyclooxygenase (COX) metabolite of arachidonic acid, a omega -6 PUFA, is a potent mediator of inflammation and cell proliferation. Dietary supplements rich in omega -3 PUFA reduce the concentrations of 2-series PG and increase the synthesis of 3 -series PG (e.g., PGE3), which are believed to be less inflammatory. However, studies on cellular consequences of increases in 3-series PG in comparison to 2-series PG have not been reported. In this study, we compared the effects of PGE2 and PGE3 on cell proliferation in NIH 3T3 fibroblasts, expression and transcriptional regulation of the COX-2 gene in NIH 3T3 fibroblasts, and the production of an inflammatory cytokine, IL-6, in RAW 264.7 macrophages. PGE3, unlike PGE2, is not mitogenic to NIH 3T3 fibroblasts. PGE2 and PGE3 both induce COX-2 mRNA via similar signaling mechanisms; however, compared with PGE2, PGE3 is significantly less efficient in inducing COX-2 gene expression. Furthermore, although both PGE2 and PGE3 induce IL-6 synthesis in RAW 264.7 macrophages, PGE3 is substantially less efficient compared with PGE2. We further show that increasing the omega -3 content of membrane phospholipid results in a decrease in mitogen-induced PGE2 synthesis. Taken together, our data suggest that successful replacement of omega - 6 PUFA with omega -3 PUFA in cell membranes can result in a decreased cellular response to mitogenic and inflammatory stimuli.
Role of Omega-3 Fatty Acids in Cognition and Inflammation. DHA is also the most abundant omega-3 fatty acid membrane lipid in the human brain [7], and plays an important role in some fundamental membrane properties including conformational flexibility, which are associated with cognitive processes [8]. This influence of DHA on conformational flexibility is due to the high number of double bonds within the structure of DHA. Changes in fatty acid composition of membranes can thus have an impact on brain functioning and such alterations have been shown to be associated with several neurodegenerative diseases, such as AD, motor system-mediated Parkinson's disease, and major depression [9].
Ischaemic stroke constitutes approximately 80% of cerebrovascular disease cases in developed countries and is the major cause of severe neurological deficits resulting in bedridden status [10]. The present treatment method for ischaemic stroke is limited to intravenous administration of recombinant tissue plasminogen activator or thrombectomy as soon as possible after the onset of stroke [11]. Effective treatments that can be administered more than 24 h after ischaemic stroke onset (during subacute phase) have not yet been established. As intracerebral inflammation lasts about 1 week after ischaemic stroke onset, it may be possible to identify therapeutic agents that would control cerebral post-ischaemic inflammation to attenuate neuronal injury and promote tissue repair in the subacute phase of ischaemic stroke [12].
In addition [13] occlusion or severe stenosis of the cerebral artery induces necrotic death of brain tissue (infarction). As well as decreasing cerebral blood flow, it inhibits protein synthesis in neurons and subsequently induces, one after another, selective expression of immediate early genes (such as c-fos, c-jun and Arc), anaerobic glycolysis, glutamate release and decrease of intracellular pH and adenosine triphosphate (ATP). In response to these ischaemic phenomena, intracellular Ca concentration rises. The activated Ca-dependent enzyme groups (proteases, phospholipases) destroy cellular membranes, resulting in mitochondrial dysfunction and cell death. Thus a major pattern of ischaemic cell death after cerebrovascular disease onset is necrosis which causes inflammation around the dead brain cells. The cellular components released from dying brain cells are recognized by infiltrating immune cells in the infarct region, which then activate immune cells to produce various inflammatory cytokines and chemokines. There are essentially two mechanism types in the immune system: adaptive immunity, which causes an immune response to a specific antigen, and innate immunity, in which the response is independent of the antigen. Therapeutic targets for ischaemic stroke could be identified by clarifying the detailed cellular and molecular mechanisms of cerebral post-ischaemic inflammation caused by innate or acquired immunity.
Conclusion: It became known to us [14] together, previous SLRs, meta-analyses, and data reported from recent clinical trials highlight a potential for omega-3s, both dietary and supplemental, in cognition outcomes in healthy populations, and in patients with SCI or MCI. The present review also indicates a possible relationship between changes in the inflammatory markers IL-6 and TNF-a and successful cognition outcomes. However, there continues to be inconsistency in cognition outcomes in omega-3 clinical trials. Important considerations for future studies should include dose, duration, and population and also measure inflammatory markers, particularly IL-6 and TNF-a, as possible indicators for improved cognition outcomes. Additional factors influencing outcomes may also include preintervention intake of omega-3s, through diet or supplementation. Also, omega-6 intake during the intervention period should be reported, as higher ratios of omega-6 to omega-3 may increase inflammation and negate beneficial effects of omega-3 interventions. Furthermore, a focus on the importance of which cognitive tests are selected to measure cognition outcomes may lead to more consistent findings. Whilst some omega-3 supplementation studies show beneficial effects on cognition and observational studies show positive associations between fish consumption and cognition, overall, there is inconsistency in findings on the effect of omega-3 fatty acids (dietary or supplemental) on cognition. With a growing body of work in this field and considerations taken from SLRs, more studies comparing the effects of dietary omega-3s and omega-3 supplementation are required to determine differences in inflammatory and cognition outcomes. Also, studies providing a comparison of the two omega-3 interventions on the relationship between inflammatory markers, such as IL-6 and TNF-a, in cognition outcomes, particularly memory domains, would provide further clarity on the role of inflammation in cognition outcomes.
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