Changes In Polyunsaturated Fatty Acids Research Articles

The Ability of Melatonin to Counteract Lipid Peroxidation in Biological Membranes

This paper reviews recent data relevant to the antioxidant effects of melatonin with special emphasis on the changes produced in polyunsaturated fatty acids located in the phospholipids of biological membranes. The onset of lipid peroxidation within cellular membranes is associated with changes in their physicochemical properties and with the impairment of protein functions located in the membrane environment. All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. These processes combine to produce changes in the biophysical properties of membranes that can have profound effects on the activity of membrane-bound proteins. This review deals with aspects for lipid peroxidation of biological membranes in general, but with some emphasis on changes of polyunsaturated fatty acids, which arise most prominently in membranes and have been studied extensively in our laboratory. The article provides current information on the effect of melatonin on biological membranes, changes in fluidity, fatty acid composition and lipid-protein modifications during the lipid peroxidation process of photoreceptor membranes and modulation of gene expression by the hormone and its preventive effects on adriamycin-induced lipid peroxidation in rat liver. Simple model systems have often been employed to measure the activity of antioxidants. Although such studies are important and essential to understand the mechanisms and kinetics of antioxidant action, it should be noted that the results of simple in vitro model experiments cannot be directly extrapolated to in vivo systems. For example, the antioxidant capacity of melatonin, one of the important physiological lipophilic antioxidants, in solution of pure triglycerides enriched in omega-3 polyunsaturated fatty acids is considerably different from that in subcellular membranes.

Changes of Polyunsaturated Fatty Acids in Human Oral Mucosa In Vivo Measured by Fourier Transform Infrared Spectroscopy

Changes of Polyunsaturated Fatty Acids in Human Oral Mucosa In Vivo Measured by Fourier Transform Infrared Spectroscopy

The effect of tyrosol, hydroxytyrosol and oleuropein on the non-enzymatic lipid peroxidation of rat liver microsomes.

The effects of the polyphenolic compounds from virgin olive oil: tyrosol, hydroxytyrosol and oleuropein on the non-enzymatic lipid peroxidation induced by ascorbate-Fe2+ of rat liver microsomes were examined. The inhibition of light emission (maximal induced chemiluminescence) by oleuropein was concentration dependent. Hydroxytyrosol showed a substantial degree of inhibition against ascorbate-Fe2+ induced lipid peroxidation in rat liver microsomes that was at least 6 times higher than that observed in the presence of oleuropein. Inhibition of lipid peroxidation by tyrosol was not observed. In rat liver microsomes incubated alone or in the presence of tyrosol, the fatty acid composition was profoundly modified when subjected to in vitro peroxidation mediated by ascorbate-Fe2+, with a considerable decrease of 18:2n6 and 20:4n6; however, changes in fatty acid composition were not observed when microsomes were incubated with hydroxytyrosol. When oleuropein was used at low concentration (5, 15 microM) a considerable decrease of 20:4n6 was observed, but 18:2n6 was not modified; at higher concentration (30, 60 microM) changes in fatty acid composition were not observed. There was a very good correlation between the presence of oxidized phospholipids and the changes in polyunsaturated fatty acids previously observed. Thus, hydroxytyrosol showed the highest protection again oxidized phospholipid formation. The presence of oleuropein at low concentration (5, 15 microM) does not prevent the formation of oxidized phospholipids (8.02 +/- 1.22 and 1.22 +/- 1.22) but concentration higher than 30 microM avoids completely the formation of this molecules whereas tyrosol at any concentration assayed was found to be ineffective and allows the formation not only of oxidized phospholipids but also of oxidized cholesterol.

Injury of rat thymocytes caused by exogenous peroxyl radicals in vitro

The aim of this study was to investigate oxidative cell injury in rat thymocytes under conditions of radical generation exterior to the cell utilizing the thermolabile azocompound 2,2′-azobis(2-amidinopropane) dihydrochloride to generate peroxyl radicals at a constant and reproducible rate. This initiator, being water-soluble and endowed with a positive charge, is suitable for studies on oxidative damage of biomembranes induced in the external water environment. The relationship between cell viability, lipid and thiol oxidation and chain-breaking antioxidant depletion was studied. During the first hour of treatment cell viability decreased slightly, protein sulfhydryl groups were consumed slowly and no significant production of conjugated dienes occurred. After 90 min of incubation, when thymocyte permeability started to increase, the concentration of α-tocopherol decreased gradually, significant changes of polyunsaturated fatty acids occurred and a rapid phase of thiol oxidation commenced. It can be concluded that, under conditions of an exogenous oxidant challenge, initially the cell membrane provides a physical barrier to the entrance of radicals to the thymocyte. When peroxyl radicals gain access to the membrane and the molecular barrier begins to disorganize, the oxidizable cellular components become susceptible to massive attack.

Human milk in disease: lipid composition.

Differences in the lipid composition of human milk have been described in maternal diseases known to affect fat metabolism. Diseases such as diabetes, cystic fibrosis, hypobetalipoproteinemia and Type I hyperlipoproteinemia affect the quantity and quality of human milk fat. Increased fatty acid chain elongation and changes in desaturation (especially delta 6 desaturase), as well as changes in lipid class composition, have been shown in diabetes and cystic fibrosis, whereas compensatory increases in medium-chain fatty acids have been described in hypobetalipoproteinemia and Type I hyperlipoproteinemia. It is important to realize that these observations were made either on single women or on very small groups of women. In infant diseases, such as breast milk jaundice and ectopic eczema, changes in polyunsaturated fatty acids in maternal milk have been described.

Malnutrition-related polyunsaturated fatty acid changes in plasma lipid fractions of cirrhotic patients

Cirrhotic patients have both impaired liver function and nutritional derangement. In fact, the prevalence of protein-energy malnutrition (PEM) is very high in these patients. The aim of the present study was to elucidate whether the nutritional status in cirrhosis could be an additional factor that would affect levels of plasma lipids. Plasma lipid phosphorus, cholesterol, and triglycerides (TG), and fatty acid profiles in plasma and plasma fractions were determined in 50 healthy subjects and 92 patients with liver cirrhosis. The cirrhotic patients were prospectively included in three groups according to the result of nutritional assessment: group 1 (n = 38), acceptable nutritional status (including well-nourished and mildly malnourished patients); group 2 (n = 29), moderate PEM; and group 3 (n = 25), severe PEM. The main findings of this study were that the decrease in plasma cholesterol and linoleic,dihomo- γ-linolenic, and arachidonic acid levels of cirrhotic patients was related to the degree of PEM. Cholesteryl esters (CE) appeared to be the most sensitive indicator of lipid changes in cirrhosis. We consider that the role of malnutrition in the changes observed for polyunsaturated fatty acid (PUFA) profiles in plasma lipids of cirrhotic patients may be of major importance, since severe malnourished subjects exhibited the lowest levels of those compounds. Dietary supplementation of both essential fatty acids (EFA) and long-chain PUFA in adequate amounts to the cirrhotic patient might be of importance in the management of the disease.

Incorporation of dietary oleate, linoleate, α-linolenate and eicosapentaenoate into the plasma lipid fractions of four strains of rat

Four strains of rat (Dark Agouti, DA; Ginger Hooded, GH; Portion, P; Hooded Wistar, HW) were fed elemental diets containing different sources of fat at the 10% (w/w) level. The dietary fats used included the following oils; olive (rich in oleate), sunflower (rich in linoleate), linseed (rich in alpha-linolenate) and fish (rich in eicosapentaenoate and docosahexaenoate). Differences between strains in response to individual diets were modest compared with the much greater differences achieved by the dietary treatments. In general, the changes in polyunsaturated fatty acid (PUFA) levels in the plasma lipids of all rat strains followed the major PUFA in the diet. There were, however, strong interactions between dietary n-6 and n-3 PUFA which affected not only the level of particular PUFA in lipid fractions but also the lipid fraction in which a particular PUFA appeared. Our findings indicate that a response to dietary fats in the plasma lipids of one strain of rat can be expected to occur with relatively minor variations in other commonly used rat strains.

Fatty acid composition of phospholipids from chick neural retina during development

The fatty acid composition of retina phospholipids from developing chicks was investigated to determine what changes, if any, occur in the relative levels of polyunsaturated fatty acids. Embryonic chicks were killed at 3-day intervals from day 6 through hatching (day 21), and at 1 week post-hatch. Fatty acids † † Fatty acids are specified by the number of carbons separated by a colon from the number of double bonds. The ‘n-’ designation indicates the number of carbons from the methyl end of the acyl chain to the nearest double bond. were prepared from retina phospholipids and were analysed by capillary gas-liquid chromatography. A comparison of the composition of yolk taken on day 6 with retinas isolated on that day revealed a much greater proportion of polyunsaturated fatty acids in the latter, suggesting an ability of the embryo to metabolize selectively unsaturated fatty acids at this early stage of development. Throughout the time course studied, saturated fatty acids constituted 50% of all fatty acids, most of which was due to palmitic acid (16:0; 33–41%). Among other saturated fatty acids, myristic acid (14:0) increased to maximal levels by day 18, then declined, while stearic acid (18:0) was minimal on day 12 and then increased. Polyunsaturated fatty acids varied between 14 and 23% of total fatty acids, depending on the developmental stage. One of the most remarkable changes in polyunsaturated fatty acids occurred in the levels of 22:4 (n-6). The proportion of this single fatty acid decreased from 9·4 to 2·4% between days 15 and 18. Relative levels of 22:5 (n-6) increased significantly between day 21 and 1 week post-hatch, from 1·1 to 3·2%. In this same time period, the proportion of 22:6 (n-3), the fatty acid known to be prominent in the outer segments of rod-dominant retinas, did not change. However, 22:6 (n-3) increased significantly from 3·8 to 9·5% between days 15 and 21, when outer segments are being formed. The fatty acid profile thus changes during development, and can be correlated with morphological stages of differentiation. The data also imply a relative enrichment of 22:6 (n-3) in the outer segment of this conedominant retina.

A rapid method for determining the oxidation of n‐3 fatty acids

The stability of unsaturated fatty acids to oxidation was monitored by following gas chromatographic (GC) analyses of headspace volatiles in comparison to changes in polyunsaturated fatty acids (PUFA) and increases in malonaldehydevia the 2‐thiobarbituric (TBA) assay. Pure standards of linoleic acid (Lo) and n‐3 fatty acids [eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)] were added to headspace vials, equilibrated in air for 10 min, followed by heating at 80°C in teflon‐capped vials for different time intervals. Headspace analysis showed increases in acetaldehyde, propenal, and propanal, corresponding to the oxidation of n‐3 fatty acids, whereas hexanal production corresponded to losses of linoleic acid. The analysis of propanal by GC‐headspace after only five minutes of heating appeared to be the most effective method of monitoring the oxidation of n‐3 fatty acids, as indicated by correlations between TBA values and loss of PUFA. The oxidation of Lo, EPA and DHA appeared to be a function of the number of double bonds. Correlations between PUFA depletion, TBA values and volatile formation indicate that under the prescribed conditions of this experiment, GC‐headspace analysis of propanal and pentane/hexanal is an excellent method for following the oxidation of selected n‐3 fatty acids and linoleic acid.

Severe changes in polyunsaturated fatty acids in the brain, liver, kidney, and retina in patients with peroxisomal disorders.

Peroxisomal disorders are a new group of congenital diseases in which peroxisomes are deficient in numbers or functionality. The prototype of these disorders is Zellweger syndrome (ZS), an extremely severe disease involving the central nervous system, liver, and kidneys (cerebro-hepato-renal syndrome). Infants with ZS have profound psychomotor retardation and hypotonia from birth, and very soon become blind and deaf. They usually die during the first year of life; autopsy examination reveals dysmyelination, gliosis, and neuronal heterotopias. Peroxisomes are absent from hepatocytes and proximal renal tubules (Goldfischer et al., 1973). The deficiencies in peroxisomal enzymes cause multiple biochemical abnormalities. In relation to lipid metabolism, there is accumulation of very long-chain fatty acids (Brown et al., 1982) due to a deficient peroxisomal s-oxidation system (Singh et al., 1984) and a decrease in plasmalogen levels (Heymans et al., 1983) attributable to a defect in dihydroxy-acetone phosphate acyltransferase (Datta et al., 1984).

Postnatal changes in polyunsaturated fatty acid (PUFA) pattern of plasma lipid components in very low birth weight infants (LBWI) receiving total parenteral nutrition (TPN) with lipids

Postnatal changes in polyunsaturated fatty acid (PUFA) pattern of plasma lipid components in very low birth weight infants (LBWI) receiving total parenteral nutrition (TPN) with lipids

Changes of polyunsaturated fatty acids in serum lipids of spontaneously hypertensive rats during the onset of high blood pressure

The fatty acid pattern of serum triglycerides and cholesterol esters has been estimated in spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) at 4,5 6 ,7, and 8 weeks of age. The percentage of linoleic acid (LA~ was lower in SHR when compared with 1AR, but increased with age in both strains. Arachidonic acid (AA) showed an abrupt fall in SHR and NR at 5 weeks of age in comparison to 4 week old rats. The fall was more pronounced in serum triglycerides of the former and in cholesterol esters of the latter. The changes in AA occured prior to the onset of hypertension in SHR. From the data it can be concluded that the formation of AA from LA might be dependent on age being quantitatively different in SHR and WR. Furthermore, eicosapentaenoic acid (EPA) appeared leaver in SHR than in age-related WR. Docosapentaenoic and docosahexaenoic acids also revealed a marked decrease in rats between 4 and 5 weeks of age indicating that individual polyunsaturated fatty acids (PUPA) change in a different manner which might be relevant to the development of high blood pressure in SHR.

Accumulation and depletion of trans octadecenoic acid in rat peripheral nerve phospholipid

The accumulation and depletion of trans 18:1 acids in the sciatic nerve phospholipids was studied in rats fed a diet containing 18% partially hydrogenated soybean oil of which 45% was trans 18:1. The nerve phospholipid of rats fed partially hydrogenated soybean oil beginning at weaning age reached a maximum incorporation of trans 18:1 of 0.8% in 4 weeks; whereas the nerve phospholipid of 18-day-old pre-weanling pups of mothers fed the partially hydrogenated soybean oil diet since their weaning contained 3.3% trans 18: l. The trans content decreased rapidly after the weaning of these second-generation rats to a steady-state level 50% higher than the maximum level reached in the first generation. Upon removal of partially hydrogenated soybean oil from the diet, the trans 18:1 of nerve phospholipid decreased much more slowly than from liver or heart phospholipid. Essential fatty acid deficiency had no influence on incorporation or removal of trans 18:1 in nerve phospholipid. The accumulation and depletion of frans 18:1 in nerve phospholipid of second-generation partially hydrogenated soybean oil-fed rats parallelled the changes of polyunsaturated fatty acids and was quite different from the changes observed in 18:0 and cis 18:1. Polyunsaturated fatty acids increased in nerve phospholipid from second but not first-generation rats fed partially hydrogenated soybean oil and declined rapidly when partially hydrogenated soybean oil was removed from the diet.

Time course of changes in fatty acid composition of gills and liver from rainbow trout (Salmo gairdneri) during thermal acclimation

AbstractRainbow trout (Salmo gairdneri), acclimated to 5°C or 20°C, were reacclimated to water of the opposite temperature. The time course of alterations in fatty acid composition of microsomes from gills and liver was monitored over a 28‐day period. Two to six days were required for maximum changes in fatty acid levels with acclimation to 20°C, whereas 10—17 days were required in the opposite direction. Fatty acids from gill microsomes had lower U/S (ratio of unsaturates to saturates) and UI (unsaturation index) and a shorter average chain length than liver microsomes; these differences were preserved with acclimation. In both tissues the U/S, UI, and chain length increased with cold adaptation and decreased with warm adaptation. In gill microsomes, changes in UI and U/S were due primarily to altered levels of saturated fatty acids and 20:4 (n‐6) and 20:5 (n‐3). The latter two acids, products of the Δ5 desaturation step in PUFA biosynthesis, also contributed to the changes in unsaturation indexes were initially mediated by large but transient changes in levels of saturates and monoenes, whereas changes in polyunsaturated fatty acids of the n‐6 and n‐3 families were delayed 3—6 days. Thus, changes in fatty acid composition that accompany acclimation to a different temperature can be resolved into those metabolic reactions (e.g., Δ5 desaturation) that are of major importance and, in the liver, into temporally more than one mechanism (e.g., altering monoenes and PUFA at different times).

Effect of Dietary Linoleate on Chick Liver Fatty Acids: Dietary Linoleate Requirement

Studies were conducted with chicks to determine changes in polyunsaturated fatty acids in liver lipids when the chicks were fed increasing amounts of dietary linoleate, and from this data the dietary requirement of the chick for linoleate was estimated. Increasing dietary amounts of linoleic acid fed to chicks as supplements of corn oil in a diet low in essential fatty acids (EFA) resulted in increased amounts of linoleate and arachidonate (18:2ω6 and 20:4ω6) and decreased amounts of eicosatrienoate (20:3ω9) in liver lipids, a characteristic of EFA deficiency. The ratio of trienoate to tetraenoate was plotted to estimate the requirement of the chick for linoleate, which was found to be 2.0% of dietary calories. The requirement estimated from the rate constant equation by computer methods was found to be the same. Equations were derived to allow an estimate of the dietary linoleate intake, based on fatty acid composition of the liver lipid.