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Biomedical subjects

D F Horrobin

Publications and source records attributed to D F Horrobin.

At least 181 records · Page 10Linked to original sources
PubMed1988

Effects of albumin on fatty acid, protein, and eicosanoid levels in rat mesenteric arterial bed perfusions.

Male rats were maintained on rat chow supplemented with 5% evening primrose oil for 2 weeks. Mesenteric perfusions were then performed, half with and half without albumin. Albumin was found to increase the yield of fatty acids and reduce eicosanoid levels. Perfusions without albumin decreased fatty acid release, increased eicosanoid levels, and showed a decrease in protein concentration over time. The value of albumin as a "trap" for fatty acids during perfusion experiments depends upon what parameter is to be measured.

Albumins↗
PubMed1988

The influence of phenelzine and tranylcypromine on the release of prostaglandins from the rat mesenteric vascular bed.

We investigated the effects of phenelzine and tranylcypromine on the release of prostacyclin, thromboxane A2, prostaglandin E2, and prostaglandin E1 from the isolated perfused rat mesenteric vascular bed. Perfusion of the preparation with phenelzine in concentrations of 15, 45, and 135 microM for 150 min led to attenuated release of all four prostaglandins measured. Inhibition generally occurred with the lowest dose used and was most prominent with the highest concentration. Tranylcypromine also decreased prostaglandin formation. However, low doses were not effective in the suppression of prostacyclin release. Both drugs had an inhibitory effect on production of prostaglandin E1, which is a metabolite of dihomo-gamma-linolenic acid, the precursor of arachidonic acid, but this was only shown to be significant with phenelzine. In this work we demonstrate that phenelzine and tranylcypromine have an inhibitory effect on the production of 2-series prostaglandins derived from arachidonic acid, and possibly a similar effect on prostaglandins of the 1-series derived from dihomo-gamma-linolenic acid.

Alprostadil↗
PubMed1988

Release of fatty acids by perfused vascular tissue in normotensive and hypertensive rats.

The release of fatty acids from perfused mesenteries of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was studied. The release of the prostaglandin precursors dihomogammalinolenic acid, arachidonic acid, and eicosapentaenoic acid was reduced in SHR when compared with age-matched WKY. The release of all other fatty acids detected in the effluent was also reduced. The differences in fatty acid release were evident even when tissue levels of the fatty acids were similar or higher in SHR than in controls. The addition of evening primrose oil and fish oil into the diet partially corrected these defects. Evening primrose oil and fish oil both attenuated increases in blood pressure, but fish oil was more potent than primrose oil. Although both diets reduced vascular reactivity, primrose oil was more effective with lower doses of norepinephrine whereas fish oil blunted the effects of both low and high doses of norepinephrine. The possible mechanisms for the effects of primrose oil and fish oil on vascular reactivity are briefly discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Plasma, platelet, and aorta fatty acids composition in response to dietary n-6 and n-3 fats supplementation in a rat model of non-insulin-dependent diabetes.

Male Sprague-Dawley rats were injected with 90 mg/kg of streptozotocin at 2 days of age. After weaning, they were put on a fat-free diet supplemented with safflower oil (S), a combination of S and linseed oil (L) or a combination of evening primrose oil (E) and L for 8 weeks. Plasma glucose levels and glycosuria were significantly elevated in all 3 groups of diabetic rats in comparison with the corresponding control rats. The percentage of arachidonic acid (20:4n-6) in plasma phospholipids of the S + L and E + L groups was similar to that of the S group and did not differ between control and diabetic rats while adrenic acid (22:4n-6) and docosahexaenoic acid (22:6n-3) changed in proportion to dietary n-3 and n-6 fats content. Arachidonic acid in aorta phospholipids significantly reduced in all 3 groups of diabetic rats as compared to the corresponding control groups. Dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid in aorta phospholipids increased by the E + L treatment. These results suggest that arachidonic acid in plasma phospholipids is kept constant regardless of the presence of diabetes of non-insulin-dependent type or dietary n-3 and n-6 fats supplementation. In aorta phospholipids, arachidonic acid in diabetic animals reduced and this may be compensated by gamma-linolenic acid supplementation, which leads to increase of dihomo-gamma-linolenic acid and arachidonic acid levels.

Animals↗
PubMed1988

Changes in human plasma essential fatty acid levels as a result of administration of linoleic acid and gamma-linolenic acid.

Administration of doses of linoleic acid (LA) up to 36 g/d in humans raised blood levels of linoleic acid but not of its metabolites. This is probably because the conversion of LA to gamma-linolenic acid (GLA) is slow and rate-limiting. We have found that administration of relatively small amounts of GLA, up to 360 mg/d, raises human blood levels of dihomogammalinolenic acid (DGLA) and arachidonic acid (AA).

Adult↗
PubMed1987

Short-term diabetes increases triacylglycerol arachidonic acid content in the rat liver.

Fatty acid compositions of liver phospholipid, cholesterol ester and triacylglycerol fractions obtained from streptozotocin-induced diabetic rats were compared to those from control or from simple-acidotic rats. Significant reductions of arachidonic acid proportions in phospholipid and cholesterol ester were found on the 3rd day after the streptozotocin treatment. In triacylglycerol, arachidonic acid and the other desaturation and elongation products of linoleic acid except for gamma-linolenic acid were increased in the diabetic rats. Although essential fatty acid composition in liver phospholipid and cholesterol ester of simple-acidotic rats did not differ from control rats, dihomo-gamma-linolenic acid, arachidonic acid, adrenic acid and docosapentaenoic acid (22:5(n - 6] contents in liver TG were significantly increased over those in control rats and were similar to those in diabetic rats. These results suggest that metabolic acidosis may contribute to the fatty acid abnormalities observed in diabetic animals.

Animals↗
PubMed1987

Effect of different ratios of dietary N-6 and N-3 fatty acids on fatty acid composition, prostaglandin formation and platelet aggregation in the rat.

Five groups of male Sprague-Dawley rats (150 g) were fed a fat-free diet supplemented with 10% by weight of evening primrose oil (Efamol, rich in linoleic acid and gamma-linolenic acid) and/or marine oil (Polepa, rich in eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) combined in several ratios (Efamol/Polepa; 10.0%/0%; 7.5%/2.5%; 5.0%/5.0%; 2.5%/7.5%; 0%/10.0%). The n-6 fatty acid levels in aortic, platelet and plasma phospholipids decreased in proportion as Efamol was replaced with Polepa. The exception in phospholipids was dihomo-gamma-linolenic acid (20:3n-6), which increased when marine oil was provided in the diet with Efamol. The ratio of 20:3n-6 to arachidonic acid (20:4n-6) was positively correlated with 20:5n-3, docosapentaenoic acid (22:5n-3) or 22:6n-3 in aortic, platelet and plasma phospholipids under these dietary conditions. In contrast, 20:3n-6 in plasma cholesterol esters, triglycerides and free fatty acids did not show any increase in the presence of Polepa. Aortic prostaglandin (PG) production (6-keto-PGF1 alpha, PGE2 and PGE1) was reduced as Efamol was progressively replaced with Polepa. Aortic PG production was positively correlated with 20:4n-6 content in aortic phospholipids. Thrombin-induced thromboxane B2 production in whole blood was related to 20:4n-6 content in platelet phospholipids. However, ADP-induced platelet aggregation was significantly decreased only in the 7.5% Efamol/2.5% Polepa group as compared to the other 4 groups. These results suggest that combined treatment with Efamol and Polepa increases the ratio of 20:3n-6 to 20:4n-6 in tissue and plasma phospholipids. An appropriate ratio of these oils favorably affects aortic PG production and platelet ADP aggregation.

Adenosine Diphosphate↗
PubMed1987

Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro.

Polyunsaturated fatty acids (PUFAs) have been shown to inhibit both normal and tumor cell growth in vitro. As PUFAs are known to induce a respiratory burst and free radical generation in polymorphonuclear leukocytes and since free radicals are toxic to cells, we investigated the effect of PUFAs on a measure of free radical generation (nitroblue tetrazolium reduction) in normal human fibroblasts and breast cancer cells in vitro. Results suggested that linoleate (LA), gamma-linolenate (GLA), arachidonate (AA) and eicosapentaenoate (EPA) can enhance nitroblue tetrazolium reduction in tumor cells but not in normal cells. GLA, AA and EPA were 1 1/2 to 2 times more effective than LA in inducing free radical generation. This difference was not due to increased uptake of LA, AA and EPA by tumor cells. In fact, the uptake of LA was the same both in normal and tumor cells whereas that of AA and EPA occurred at approximately half the rate in the tumor cells compared to normal cells. This indicates that PUFA induced growth inhibition and cytotoxicity to tumor cells may, at least in part, be due to enhanced free radical generation.

Breast Neoplasms↗
PubMed1987

Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent, and impulsive offenders.

Plasma phospholipid essential fatty acids and some of their main metabolites, prostaglandins, were measured among habitually violent and impulsive male offenders, who all had alcohol abuse problems, and nonviolent control persons. Linoleic acid (18:2n-6), the precursor of the n-6 fatty acids, was below normal in intermittent explosive disorder, but the dihomogammalinolenic acid (DGLA) (20:3n-6) and some subsequent n-6 acids were at the same time elevated among all offenders. Also, a monounsaturate, oleic acid (18:1n-9) was elevated. The high DGLA correlated with low cholesterol level in intermittent explosive disorder. The arachidonic acid metabolites PGE2 and TxB2 were elevated in violent antisocial personality. The PGE1/DGLA ratio was low in intermittent explosive disorder. The number of registered violent crimes and violent suicidal attempts correlated with high phospholipid DGLA values. The possibility that the high phospholipid DGLA is connected with low free DGLA pool, and therefore low PGE1 formation, among these offenders is discussed.

8,11,14-Eicosatrienoic Acid↗
PubMed1987

The role of linoleic acid and its metabolites in the lowering of plasma cholesterol and the prevention of cardiovascular disease.

An increase in linoleic acid intake lowers plasma cholesterol and is one of the safest methods for achieving this end. However, the amounts that must be consumed are large. Linoleic acid is metabolized via several routes and it is probable that a metabolite, rather than linoleic acid itself, is responsible for the cholesterol-lowering effect. If that metabolite could be identified, safe, drug-free, cholesterol-lowering might be achieved with much lower doses. Evidence is reviewed which suggests that a long-chain polyunsaturated fatty acid and/or a prostaglandin metabolite may be responsible for the cholesterol-controlling action of linoleic acid. Such metabolites may be effective also in controlling other risk factors for cardiovascular disease, such as elevated blood pressure and enhanced platelet aggregation. Epidemiological studies suggest that low levels of those metabolites, especially dihomogammalinolenic acid and arachidonic acid, are powerful independent risk factors for development of ischaemic heart disease. Further research in this area is urgently needed now that it is broadly accepted that cholesterol-lowering does indeed reduce the risk of cardiovascular disease.

Cardiovascular Diseases↗
PubMed1987

The influence of dietary marine oil (Polepa) and evening primrose oil (Efamol) on prostaglandin production by the rat mesenteric vasculature.

The interactions of n-6 and n-3 fatty acids on prostaglandin metabolism in the isolated rat mesenteric vessels were studied. Sprague-Dawley rats (200-220 g) were fed for two weeks a fat-free semi-synthetic diet supplemented with 10% by weight of different combinations of Evening Primrose Oil (Efamol), a rich source of linoleic acid (LA) and gamma-linolenic acid (GLA), the immediate precursor of dihomo-gamma-linolenic acid (DGLA), and Polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The combinations of supplement were as follows: 9% Efamol - 1% POL, 8% Efamol - 2% POL, 7% Efamol - 3% POL, 6% Efamol - 4% POL, 5% Efamol - 5% POL. The outflow of thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), PGE2, and PGE1 was decreased in relation to the proportion of marine oil in the diet, except for the group which received 8% Efamol - 2% POL, and which showed an increase in 6-keto-PGF1 alpha, PGE2, and PGE1. The decrease in TxB2 was much greater than those of 6-keto-PGF1 alpha or PGE2, while PGE1 followed the same pattern as prostacyclin and PGE2. These results suggest that n-3 fatty acids, at high concentrations, inhibits conversion of both DGLA and AA to eicosanoids. Low concentrations of fish oil may, in contrast, increase formation of desirable 1 and 2 series eicosanoids.

Administration, Oral↗
PubMed1987

Low prevalences of coronary heart disease (CHD), psoriasis, asthma and rheumatoid arthritis in Eskimos: are they caused by high dietary intake of eicosapentaenoic acid (EPA), a genetic variation of essential fatty acid (EFA) metabolism or a combination of both?

The low prevalences of CHD, psoriasis, asthma and rheumatoid arthritis in Eskimos have been attribute to the high dietary intake of EPA from fish and marine mammals. However, even on a Western diet, Eskimos have plasma arachidonic acid (AA) levels far below those seen in Europeans while dihomogammalinolenic acid (DGLA) levels are higher in Eskimos. These low AA and high DGLA levels seem to be due to a genetic abnormality in EFA desaturation since they are found even when EPA intakes are low. Since AA is known to be important in the pathogenesis of CHD, asthma, psoriasis and arthritis, while DGLA has properties which make it of likely therapeutic value in these conditions, the genetically high DGLA and low AA are likely to be as important as dietary EPA in determining Eskimo disease patterns.

Arthritis, Rheumatoid↗
PubMed1987

Uptake and distribution of cis-unsaturated fatty acids and their effect on free radical generation in normal and tumor cells in vitro.

We have previously shown that cis-unsaturated fatty acids (c-UFAs) possess a selective tumoricidal action that can be blocked by antioxidants. This property of c-UFAs might be due to various factors, including increased uptake, unusual distribution, or an ability to alter free radical generation in tumor but not normal cells. 14C-labelled linoleic acid (LA) uptake was almost the same in normal and tumor cells, whereas that of 14C-labelled arachidonic acid (AA) and 14C-labelled eicosapentaenoic acid (EPA) in tumor cells was substantially less than in normal cells. Tumor cells incorporate major portions of the fatty acids in the ether lipid and phospholipid fractions, whereas normal cells incorporate the fatty acids primarily in the phospholipid fraction. LA, AA, and EPA augmented nitroblue tetrazolium reduction, an indication of free radical generation, selectively in the tumor cells. These results suggest that there are significant differences between normal and tumor cells in fatty acid uptake and distribution, and in the ability of fatty acids to generate free radicals.

Animals↗
PubMed1987

Impaired platelet aggregation and thromboxane generation in essential fatty acid-deficient rats.

ADP-induced platelet aggregation and thrombin-induced thromboxane B2 generation in diluted whole blood from rats fed a fat-free diet supplemented with 10% (by weight) hydrogenated coconut oil [essential fatty acid (EFA) deficient] were significantly lower than that in animals fed 10% safflower oil [(SFO) rich in linoleic acid] or 10% marine oil (rich in eicosapentaenoic acid and docosahexaenoic acid). Plasma fibrinogen levels were significantly lower and liver function was impaired in the EFA-deficient group compared with the other two groups. Platelet responsiveness to ADP was restored when plasma from the EFA-deficient rats was replaced by plasma obtained from rats fed a nonpurified diet. ADP responsiveness and thrombin-stimulated thromboxane B2 production in diluted whole blood were also restored after 2 wk of injections of 100 mg ethyl linoleate every 48 h, and partially restored by injections of 100 mg ethyl alpha-linolenate. When ADP-induced platelet aggregation was examined in washed platelets, the impaired ADP aggregation (found when platelets of the EFA-deficient rats were suspended in their own plasma) was not observed at either high (9.5 microM) or low (1.0 microM) ADP concentrations. Although thrombin-stimulated thromboxane B2 production in washed platelets in the EFA-deficient rats was lower than that in the SFO-fed rats, the magnitude of aggregation was not different. In addition, inhibition of thrombin-induced platelet aggregation by apyrase (0.06 U/mL) was identical in the two groups. These results suggest that impaired platelet aggregation in EFA deficiency is related more to plasma factors than to inherent platelet properties and that restoration of normal liver function is associated with normal platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1987

Essential fatty acids, prostaglandins, and alcoholism: an overview.

Essential fatty acids (EFAs) are major structural components of the brain and through their effects on membrane properties can influence nerve conduction, transmitter release, and transmitter action. Prostaglandins (PGs) derived from EFAs have profound behavioral effects and are also able to modify conduction and transmitter function. Effects of alcohol on EFAs and PGs are therefore good candidates for explaining at least some of the actions of alcohol on brain function. Ethanol has three main known actions on EFA and PG metabolism: it reduces blood linoleic acid levels and induces or exaggerates EFA deficiency states; it blocks metabolism of linoleic acid to EFA metabolites which are known to be important in brain structure; and it enhances conversion of the linoleic acid metabolite, dihomo-gamma-linolenic acid, to PGE1. This review demonstrates that some of the short-term behavioral effects of ethanol and some of its long-term adverse effects on brain, liver, and other tissues may be partly explicable in terms of ethanol actions on EFA and PG metabolism. Modification of such metabolism by dietary and other means has already been shown to influence the effects of alcohol and alcohol withdrawal in both humans and animals. This promises to be a fruitful source of investigation with substantial implications for the understanding and treatment of alcoholism.

Alcoholism↗
PubMed1987

Effect of dietary cholesterol and polyunsaturated fats on plasma and liver lipids in guinea pigs.

Weanling male Hartley guinea pigs were fed for 6 weeks on a regular chow supplemented with 5% polyunsaturated fats (safflower, linseed, or evening primrose oil) or 5% saturated fats (hydrogenated coconut oil) with or without the addition of 1% cholesterol to the diet. Cholesterol feeding resulted in slower growth, hyperlipidemia, and a fatty liver. Cholesterol contents (predominantly in the form of cholesterol esters) in plasma and liver were increased, but the increase of plasma cholesterol was significantly reduced when unsaturated fats in place of saturated fat were added to the diet. The essential fatty acid contents in plasma and liver lipids were modulated by the dietary fats and by the cholesterol feeding. The latter reduced the proportions of 20:4 (n-6), but increased or had no effect on the levels of 18:2 (n-6). These results led to a reduced ratio of 20:4 (n-6)/18:2 (n-6), suggesting that cholesterol feeding may impair the desaturase activities.

Animals↗
PubMed1987

Long-term ethanol consumption in the hamster: effects on tissue lipids, fatty acids and erythrocyte hemolysis.

Male Golden Syrian hamsters at 1 year of age were given a basal diet and either distilled water or 10% absolute ethanol in distilled water to drink for 1 year in order to determine the influence of prolonged ethanol intake on tissue long chain fatty acid, lipid composition and erythrocyte hemolysis in response to osmotic stress. Total lipids were extracted from liver, heart, plasma and erythrocytes. Individual lipid fractions were quantitated and the percentage fatty acid composition of the lipid fractions analyzed by gas-liquid chromatography. Although no significant changes in tissue lipid content or erythrocyte hemolysis were attributable to ethanol intake, fatty acid changes were marked in the ethanol-fed hamsters. The primary fatty acid changes were increased oleic acid (40-50%) and decreased linoleic acid (25-60%) which were observed in all tissues. Arachidonic acid was decreased only in triacylglycerol fractions. The results suggest that in the hamster long-term voluntary ethanol intake alters specific long chain fatty acids, but that erythrocyte membrane integrity and tissue lipid composition were not compromised.

Alcohol Drinking↗