Fatty acids, lipid peroxidation and diseases (original) (raw)
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Non enzymatic metabolites of polyunsaturated fatty acids: friend or foe
OCL, 2015
Under condition of oxidative stress, free radical mediated peroxidation of polyunsaturated fatty acids generates in vivo, cyclic metabolites like the isoprostanes, neuroprostanes, dihomo-isoprostanes, isofuranes among a large number of key products which participate in many pathophysiological processes. These metabolites display a wide range of biological actions, and some of them are now the most reliable indicators of oxidative stress in humans. In this review, we will discuss several key points of our understanding of those cyclic polyunsaturated fatty acids derivatives, going from multi-step syntheses, analytical chemistry and biological activities. Keywords: biomarkers / polyunsaturated fatty acid / radical peroxidation / isoprostanes / neuroprostanes / isofurans / total synthesis Résumé-La peroxydation radicalaire des acides gras polyinsaturés, constituants majeurs des membranes cellulaires, conduit à de nombreux métabolites, comme les isoprostanes, les neuroprostanes, les dihomo-isoprostanes, les isofuranes. Certaines isoprostanes sont à présent des marqueurs du stress oxydant cellulaire les plus significatifs utilisés en clinique. Ces lipides oxygénés possèdent également un large spectre d'activités biologiques. Cette revue fera le point sur notre dernière stratégie de synthèse organique multi-étapes pour obtenir ces molécules pures et sur des résultats récents issus de collaborations avec des collègues biologistes et cliniciens.
Polyunsaturated fatty acids in health and disease
Polyunsaturated fatty acids (PUFAs) are necessary for overall health. Two PUFAs families, n-6 and n-3 fatty acids, are physiologically and metabolically distinct. The proportion of PUFAs in serum and erythrocyte phospholipids, which depends on endogenous metabolism controlled by genetic polymorphisms and dietary intake, is an important determinant of both health and disease. Both n-3 and n-6 PUFAs are processed to powerful promoters of eicosanoids synthesis at the cyclooxygenase and lipoxygenase level. Evidence from observational and intervention studies suggest that n-3 PUFAs are cardioprotective, perhaps through their anti-inflammatory, anti-arrhythmic, lipid-lowering and antihypertensive effects. In contrast, dietary n-6 PUFAs have proinflammatory effects. Low n-3 and elevated n-6 PUFAs levels were found in patients with cancer on different sites. The present review focuses on current knowledge related to PUFAs intake and status in health and disease, with reference to the Serbian population.
Biological and Pharmaceutical Bulletin, 2003
Epidemiologic studies have shown an apparent beneficial effect of fish oil containing high levels of n-3 polyunsaturated fatty acids (PUFA) on mortality from heart disease and cancer. 1,2) The undesirable effects of high fish oil intake have none the less been a concern, because n-3 PUFA are more readily oxidized under atmospheric conditions. 3) Many earlier studies have suggested that a diet containing high levels of fish oil enhances lipid peroxidation in the organs, blood, and urine of experimental animals and humans (references cited in references 4,5)). In contrast, we have demonstrated that there are no deleterious effects of fish oil feeding on lipid peroxidation of rat erythrocyte membranes 4) and rat organs, 5) whereas the degree of lipid peroxidation of erythrocyte membranes in the fish oil diet group were markedly higher than that of the safflower oil diet group when the in vitro oxidation was induced under atmospheric conditions. 4) It has been assumed that when oxidative stress is generated in living bodies, lipid peroxidation is induced to mediate DNA damage. Many in vitro studies have shown that peroxidized lipids mediate DNA damage as assessed by DNA chain breaking 6-10) and 8-hydroxydeoxyguanosine (8-OHdG) formation. 11-14) Hence supplementation of fish oil with high n-3 PUFA, which are more susceptible to oxidative stress than n-6 PUFA, has been thought to enhance oxidative stress-induced DNA damage. However, there is no evidence showing that lipid peroxidation enhances oxidative stress-induced DNA damage. The present study was undertaken to determine whether n-3 PUFA-rich diet supplementation enhances oxidative stressinduced DNA damage and whether lipid peroxidation mediates oxidative stress-induced DNA damage. Hepatocytes isolated from rats fed an n-3 PUFA-rich fish oil diet and an n-6 PUFA-rich safflower oil diet (control) were subjected to in vitro oxidative stress. MATERIALS AND METHODS Materials ADP monopotassium salt was obtained from Oriental Yeast Co. (Tokyo, Japan). Pentobarbital sodium salt was obtained from Dainippon Pharmaceutical (Osaka, Japan). Trypsin inhibitor (type II-S, from soybean), bovine serum albumin (BSA), cytochrome c (from horse heart), catalase [EC 1.11.1.6] (from bovine liver), alkaline phosphatase type III [EC 3.1.3.11] (from Escherichia coli), luminol, and Triton-X 100 were purchased from Sigma Chemical Company (St. Louis, MO, U.S.A.). DL-a-Tocopherol was from Tokyo Chemical Industry (Tokyo, Japan). Thiobarbituric acid (TBA) was obtained from Nacalai Tesque (Kyoto, Japan). 2-[4-(2-Hydroxyethyl)-1-piperzinyl]ethanesufonic acid (HEPES), O,O-bis(2-aminoethyl)-ethyleneglycol N,N, NЈ,NЈ-tetraacetic acid (EGTA) and EDTA disodium salt were obtained from Dojindo Laboratories (Kumamoto, Japan). Phosphatidylcholine (PC) (from egg yolk) was obtained from Funakoshi Co. Ltd. (Tokyo, japan), and phosphatidylethanolamine (PE) (from egg yolk) was obtained from Taiyo Kagaku Co. Ltd. (Tokyo, Japan). PC hydroperoxide (PCOOH) and PE hydroperoxide (PEOOH) were prepared immediately before use according to a method described elsewhere. 15,16) Briefly, PC and PE were photooxidized at 10°C for 10 h in the presence of methylene blue, and methylene blue was removed by passing through a column of florisil. Peroxide values of PCOOH and PEOOH were estimated to be 3000 and 2700 neq/mg, respectively. Other reagents were obtained from Wako Pure Chemical Industries
Dietary intakes of polyunsaturated fatty acids and indices of oxidative stress in human volunteers
European Journal of Clinical Nutrition, 1999
Objective: To assess whether nutritionally-relevant changes in polyunsaturated fatty acid (PUFA) intake alter indices of oxidative stress in human volunteers Design: A split plotachange over dietary study where half the volunteers consumed a diet containing 5% PUFA (low PUFA) as food energy for 4 weeks and after a 6 week washout period consumed a 15% PUFA (high PUFA) diet for another 4 weeks. The second group of volunteers completed this protocol in reverse. Total fat, carbohydrate, protein and vitamin E contents of the diets were constant. Subjects: 10 healthy, non-smoking, male volunteers aged 32.6 AE 1.7 y Results: There was a signi®cant increase in whole blood oxidised glutathione (P`0.05), an index of oxidative stress, after consumption of the high PUFA diet. Moreover, urinary thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, signi®cantly increased (P 0.038) following consumption of the high PUFA diet and decreased (P 0.031) after consuming the low PUFA diet. However, there was no change in non speci®c plasma indices of lipid peroxidation, conjugated dienes and TBARS, nor in red cell antioxidant enzymes glutathione peroxidase, glutathione reductase, and catalase. However, superoxide dismutase signi®cantly decreased (13%, P 0.018) after consumption of the low PUFA diet. Total cholesterol increased by 13% (P 0.014) after consumption of the low PUFA diet. Conclusions: This study indicates that although increasing dietary levels of PUFA may favourably alter cholesterol pro®les, the same dietary changes may adversely affect some indices of lipid peroxidation. Care should be taken when providing dietary advice on PUFA intake and an adequate intake of antioxidants to match any increased PUFA may be important for preventing oxidative stress.
Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies
Linoleic and alpha-linolenic acids, obtained from plant material in the diet are the precursors in tissues of two families with opposing effects which are referred to as "essential fatty acids" (EFA): arachidonic acid (AA) and pentaene (eicosapentaenoic acid: EPA) and hexaene (docosahexaenoic acid: DHA) acids. The role of EFA is crucial, without a source of AA or compounds which can be converted into AA, synthesis of prostaglandins (PGs) by a cyclooxygenase (COX) enzyme would be compromised, and this would seriously affect many normal metabolic processes. COX, also known as prostaglandin endoperoxide synthase (Pghs) or as prostaglandin G/H synthase, is a key membrane bound enzyme responsible for the oxidation of AA to PGs. Two COX isoforms have been identified, COX-1 and COX-2 that form PGH 2 , a common precursor for the biosynthesis of thromboxane A 2 (TxA 2), prostacyclin (PGI 2) and PGs (PGD 2 , PGE 2 , PGF 2α. COX-1 enzyme is expressed constitutively in most cells and tissues. Its expression remains constant under either physiological or pathological conditions controlling synthesis of those PGs primarily involved in the regulation of homeostatic functions. In contrast, COX-2 is an intermediate response gene that encodes a 71-kDa protein. COX-2 is normally absent from most cells but highly inducible in certain cells in response to inflammatory stimuli resulting in enhanced PG release. PGs formed by COX-2 primarily mediate pain and inflammation but have multiple effects that can favour tumorigenesis. They are more abundant in cancers than in normal tissues from which the cancers arise. COX-2 is a participant in the pathway of colon carcinogenesis, especially when mutation of the APC (Adenomatous Polyposis Coli) tumour suppressor gene is the initiating event. In addition, COX-2 up-regulation and elevated PGE 2 levels are involved in breast carcinogenesis. It seems that there is a correlation between COX-2 level of expression and the size of the tumours and their propensity to invade underlying tissue. Inhibition by non-steroidal anti-inflammatory drugs (NSAIDs) of COX enzymes which significantly suppress PGE 2 levels, reduced breast cancer incidence and protected against colorectal cancer. Therefore it is suggested that consumption of a diet enriched in n-3 PUFA (specifically EPA and DHA) and inhibition of COX-2 by NSAIDs may confer cardioprotective effects and provide a significant mechanism for the prevention and treatment of human cancers.
2021
Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (n = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.5% fish oil + 200 mg/kg vitamin E. Antioxidants (enzymatic and non-enzymatic), oxidative status (malondialdehyde and isoprostanoids), and n-3 and n-6 PUFAs of tissues were analysed. A chain mechanism of oxidant/antioxidant molecules, which largely depended on the particular PUFA composition, was delineate...
Synthesis and Functional Significance of Poly Unsaturated Fatty Acids (PUFA's) in Body
Synthesis and Functional Significance of Poly Unsaturated Fatty Acids (PUFA’s) in Body, 2018
There are 2 types of polyunsaturated acids (PUFA's) namely omega 6 and omega 3 series. PUFA's possess amphipathic properties i.e. hydrophobic head and hydrophilic tail. Such structure besides other properties of unsaturated fatty acids cause biological action especially maintaining cell membrane fluidity inhibiting inflammatory processes, decreasing secretion of proinflammatory cytokines by monocytes and macrophages/reducing susceptibility to ventricular rhythm disorders of the heart, improving functions of the vascular endothelial cells, inhibiting blood platelet aggregation and reducing triglyceride synthesis in the liver. In an organism arachidonic acid (ARA) gets converted to prostanoid series (PGE2, PGI2, TXA2) and leukotrienes (LTB4, LTC4, LTD4) which have proinflammatory potential and can induce platelet aggregation and vasoconstriction. The metabolism of EPA and DHA gives prostanoid series (PGE3, PGI3, TXA3) and leukotriene series (LTB5, LTC5, LTD5), this group of eicosanoids show anti-inflammatory and antiarrhythmic properties.
Balance between polyunsaturated fatty acids and antioxidants in nutrition
Lipid Technology, 2008
It is recommended that humans increase their consumption of omega-3 polyunsaturated fatty acids (PUFA) because of many nutritional advantages. However, the oxidative instability of these fatty acids poses a problem regarding the sensory and nutritional quality of foods. It is clear that antioxidants need to be added to stabilize these lipids during food processing and storage, as well as to provide the body with enough antioxidant power to counteract any oxidative stress resulting from the increased intake of PUFA. However, we need more knowledge regarding the levels of antioxidant required for food stability and nutritional adequacy as well as the nature of antioxidant oxidation products and their toxicological significance.
The Journal of Nutritional Biochemistry, 1996
The intake of (n-3) long chain polyunsaturated fatty acids (LCPs) have beneficial effects on cardiovascular diseases, renalfinction, and physiology of retina and brain in human neonates. Several authors recently reported a correlation between tissue 20:4(n-6) status and neonatal growth. Incorporation of highly unsaturated fatty acids into tissue phospholipids may enhance peroxidation of cellular membranes. We fed weanling rats with a 10% fat diet that provided lB:l(n-9), 18:2(n-6) and 18:3(n-3) in a similar ratio to that of rat milk (group A), and with a diet supplemented with (n-3) LCPs (group B), or with (n-6) and (n-3) LCPs (group C), and studied the effects of diet on lipid peroxidation of erythrocyte membranes, liver microsomes and brain homogenates, and hepatic and cerebral activities of antioxidant enzymes. Alterations in tissue fatty acid composition were not paralleled by significant changes in activities of antioxidant enzymes or vitamin E content in liver microsomes. Total and reduced glutathione levels in liver homogenates were significantly higher in groups B and C compared with group A. Tissue lipids in groups B and C were more susceptible to induced peroxidation than in group A. Maximal formation of lipid peroxidation products was observed in erythrocyte membranes and liver microsomes in group C. These results may have implications on the optimal design of infant formulas based on (n-3) and (n-6)
Polyunsaturated Fatty Acids: Impact on Health and Disease Status
Life and Science
Over the last decades, the polyunsaturated fatty acids (PUFAs) have been largely explored not only for their nutritional value but also for the numerous biological functions and therapeutic effects. The serum and erythrocyte levels of PUFAs depend on the genetic control of metabolism as well as the dietary intake and are considered to reflect the health and disease status of an individual. Two families of PUFAs, omega-3 (n-3) and omega-6 (n-6), have gained much attention because of their involvement in the production of bioactive lipid mediators and therefore, a balanced omega-6/omega-3 ratio is crucial in maintaining the overall health of an individual. Omega-3 PUFAs, notably eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have been shown to exert beneficial effects, possibly due to their lipid-lowering, anti-inflammatory, anti-hypertensive and cardioprotective effects, whereas omega-6 fatty acids such as arachidonic acid (ARA, 20:4n-6) exhibit the oppo...