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Biomedical subjects

D F Horrobin

Publications and source records attributed to D F Horrobin.

At least 163 records · Page 9Linked to original sources
PubMed1989

Effect of essential fatty acid depletion on tissue phospholipid fatty acids in spontaneously hypertensive and normotensive rats.

Weanling male spontaneously hypertensive (SHR) and normotensive (WKY) rats were maintained on a fat-free semisynthetic diet and killed at various intervals. The effects of fat-depletion on the appearance of essential fatty acid (EFA) deficiency symptoms, the progressive changes of major fatty acids in plasma, liver, heart, and kidney phospholipids (PL), and in skin total lipids were compared between these two strains. After five weeks on the diet, the slower growth and the appearance of EFA deficiency symptoms became evident in SHR. In general, fat-depletion reduced the levels of n-6 fatty acids, whereas it increased those of 20:3n-9. However, the fat-depletion induced reduction of 18:2n-6 in heart PL and 20:4n-6 in kidney, while the elevation of 20:3n-9 in plasma, heart, and kidney PL were greater in WKY than in SHR. As a result, the elevation of biochemical EFA deficiency index--20:3n-9/20:4n-6 ratio--was greater in WKY than in SHR. In comparison with WKY, the concentrations of liver triacylglycerols and the weights of adipose tissues in SHR were reduced to a greater extent, indicating an active catabolism of triacylglycerols in SHR. This study suggests that the earlier appearance of morphological symptoms of EFA deficiency in SHR was not associated with the reducing n-6 EFA levels or with an elevation of triene/tetraene ratio, but possibly to a reduced supply of n-6 EFA for skin prostaglandin synthesis.

Animals↗
PubMed1989

The effect of dietary n-6 and n-3 polyunsaturated fatty acids on blood pressure and tissue fatty acid composition in spontaneously hypertensive rats.

Effects of dietary n-6 and n-3 fatty acids (FAs) on blood pressure (BP) and tissue phospholipid (PL) FA composition in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. Male weanling SHR and WKY were fed a fat-free semisynthetic diet supplemented with 10% (w/w) fats containing (a) 78% 18:2n-6 (LA-rich), (b) 20% LA and 55% 18:3n-3 (LN-rich), or (c) 11% LA and 3% LN (CON) for seven weeks. Dietary fats did not affect the BP elevation, but significantly altered the FA composition of brain, adrenal gland, renal medulla and cortex PL in SHR. The LA-rich diet increased n-6 FA while it reduced n-3 FA levels. The levels of 20:4n-6 were not significantly different between animals fed the LA-rich and the CON diets. LN-rich diet increased the levels of n-3 FAs, while it reduced those of n-6 FAs. However, the extent of change was significantly less in SHR than in WKY. In all dietary groups, SHR, as compared to WKY, had a relatively higher level of the 2 series prostaglandin (PG) precursor, 20:4n-6, and a relatively lower level of the 1 and 3 series PG precursors, 20:3n-6 and 20:5n-3. The possibility that the unbalanced eicosanoid FA precursor levels might contribute to the development of hypertension in this animal model is discussed.

Adrenal Glands↗
PubMed1989

A double-blind trial of essential fatty acid supplementation in patients with tardive dyskinesia.

This study reports the results of a trial of essential fatty acid (EFA) supplementation in psychiatric patients (predominantly schizophrenics) with movement disorders. Evidence of EFA deficiency in these patients was observed. The antidyskinetic effect of EFA supplementation was marginally significant but not clinically important. However, active treatment produced highly significant improvements in total psychopathology scores and schizophrenia subscale scores, and a significant improvement in memory.

Antipsychotic Agents↗
PubMed1989

Plasma fatty acid levels in patients with acquired immune deficiency syndrome and in controls.

Polyunsaturated fatty acids (PUFAs) are known to modulate the immune system in vivo and to inactivate envelope viruses in vitro. Patients with AIDS had low total plasma lipid levels and low levels of a number of individual fatty acids. However, the C20 and C22 essential fatty acids of the n-3 series were selectively and highly significantly reduced. Normalization of these fatty acid levels in AIDS patients may be a worthwhile therapeutic aim.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The prostaglandin outflow from perfused mesenteric vasculature of rats fed different fats.

The effects of dietary n-6 polyunsaturated fatty acids and replacement with saturated fat or fish oil on the prostaglandin outflow from perfused mesenteric vasculature in rats were studied. Seventy-two weanling male rats were fed ad libitum a semi-synthetic diet supplemented with 10% by weight of oil, composed wholly of n-6 fatty acid-rich evening primrose oil, or replaced partly or completely (25, 50, 75 or 100%) by n-6 fatty acid-deficient fish oil or hydrogenated coconut oil for 8 weeks. The outflows of 6-keto-PGF1 alpha, thromboxane B2, and prostaglandin E from the perfused mesenteric vasculature were measured at 60 min-time point after starting the perfusion. In general, the release of prostanoids from the mesenteric vasculature was significantly reduced in rats fed a diet in which evening primrose oil was partly or completely replaced by either hydrogenated coconut or fish oil. This was probably due to the insufficient conversion of linoleic acid to arachidonic acid. The extent of reduction was greater in fish oil-fed than in hydrogenated coconut oil-fed rats, while the levels of arachidonic acid in aortic phospholipids were similar between these two groups. This result implies that the greater reduction of prostaglandin synthesis in rats fed fish oil was due to the inhibitory effect of eicosapentaenoic and docosahexaenoic acids in fish oil on the conversion of arachidonate to eicosanoids.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Essential fatty acids in clinical dermatology.

A deficiency of essential fatty acid intake can produce severe cutaneous abnormalities but is exceedingly rare in clinical practice. Recent research has shown that abnormalities in essential fatty acid metabolism may play a role in atopic eczema, acne, and psoriasis. Therapeutic innovations have already resulted from this knowledge, and more are likely to emerge.

Acne Vulgaris↗
PubMed1989

Essential fatty acid and lipid profiles in plasma and erythrocytes in patients with multiple sclerosis.

This study was conducted to investigate the possible differences in erythrocyte lipid composition, which might account for the previously reported increase in erythrocyte membrane zinc levels in patients with multiple sclerosis (MS). Compared with healthy control subjects, plasma lipids in patients with MS contained less sphingomyelin but more phosphatidylserine and the cholesterol-phospholipid ratio was 42% higher in the plasma from MS patients (p less than 0.01). In erythrocytes from MS patients, phosphatidylinositol was lower and erythrocyte cholesterol per milligram protein was significantly lower than concentrations in healthy control subjects (p less than 0.01). Among the long-chain fatty acids, the omega-3 fatty acids were lower in plasma from MS patients and linoleic acid was lower in erythrocyte ghosts from MS patients (p less than 0.01). We conclude that altered levels of cholesterol in plasma and erythrocytes from MS patients may contribute to increased erythrocyte-membrane Zn in MS patients. It cannot be stated with certainty whether the altered fatty acid profiles in MS patients were a function of the disease or of altered fatty acid intake.

Cholesterol↗
PubMed1989

Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response.

Gamma-linolenic acid in the form of a particular variety of evening primrose oil (Epogam) has been reported of value in the treatment of atopic eczema. Nine controlled trials of evening primrose oil were performed in eight centres. Four of the trials were parallel and five cross-over. Doctors and patients assessed the severity of eczema by scoring measures of inflammation, dryness, scaliness, pruritus and overall skin involvement. Individual symptom scores were combined to give a single global score at each assessment point. In the analysis of the parallel studies, both patient and doctor scores showed a highly significant improvement over baseline (P less than 0.0001) due to Epogam: for both scores the effect of Epogam was significantly better than placebo. Similar results were obtained on analysis of the cross-over trials, but in this case the difference between Epogam and placebo in the doctors' global score, although in favour of Epogam, failed to reach significance. The effects on itch were particularly striking. There was no placebo response to this symptom, whereas there was a substantial and highly significant response to Epogam (P less than 0.0001). When the improvements, or otherwise, in clinical condition were related to changes in plasma levels of dihomogammalinolenic and arachidoni acids, it was found that there was a positive correlation between an improvement in clinical score and a rise in the fatty acid levels.

Adolescent↗
PubMed1989

Fatty acid changes in liver choline and ethanolamine glycerophospholipids in aspirin-treated rats fed linoleate, gamma-linolenate and fish oil.

The effects of dietary linoleic acid, gamma-linolenic acid and marine fatty acids on the development of aspirin-induced gastric hemorrhage and the distribution of liver glycerophospholipid fatty acids in fat-deficient growing rats were studied. Aspirin (100 mg/day)-treated and nontreated rats were fed for 7 days, a mixed diet of 2.5% safflower oil and 7.5% hydrogenated coconut oil (SFO/HCO) or 7.5% fish oil (SFO/FO), or 2.5% gamma-linolenate concentrate and 7.5% fish oil (GLA/FO). Gastric hemorrhage was induced in animals by aspirin treatment to various extents. It was not affected by FO feeding, but was significantly alleviated by GLA feeding. Aspirin treatment reduced the proportions of 20:4n-6 in liver phosphatidylcholine. FO feeding (in SFO/FO and GLA/FO rats) further reduced the 20:4n-6 level and replaced it by n-3 fatty acids. GLA feeding, on the other hand, elevated the proportion of 20:4n-6. As a result, the reduction of 20:4n-6 by fish oil feeding, was less significant in GLA/FO rats than in SFO/FO rats. The degree of gastric hemorrhage appeared to relate negatively to the levels of 20:4n-6 in liver phosphatidylcholine, and to the sum of 20:4n-6 and 20:5n-3 when FO was included in the diet. It is suggested that long-chain polyunsaturated fatty acids (20:4n-6 and 20:5n-3) per se in addition to being precursors of prostaglandins, may also affect the development of gastric hemorrhage, possibly by modulating the permeability of cell membranes in the gastric mucosa.

Animals↗
PubMed1988

Prostaglandin E1: physiological significance and clinical use.

Contrary to popular belief, prostaglandin (PG) E1 and its immediate precursor, dihomogammalinolenic acid (DGLA), are found in physiologically important amounts in humans. PGE1 has many desirable effects, particularly with regard to the cardiovascular system and to inflammation. PGE1 is difficult to use therapeutically because of its short life. Better clinical results may be obtained by administering its precursors such as DGLA and gamma-linolenic acid (GLA).

Alprostadil↗
PubMed1988

Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation.

The contribution of lipid peroxidation to the killing of human breast cancer cells by gamma-linolenate (GLA) was examined. Other fatty acids of different cytotoxic potential containing 2, 4, 5, and 6 double bonds were also tested for comparison. It was found that the cytotoxic potential varied with the ability of the fatty acids to stimulate the production of superoxide radicals. Neither hydrogen peroxide nor hydroxy radicals are significantly involved in cell killing. As nonspecific indicators of lipid peroxidation, measurements of the loss of unsaturated fatty acid in the phospholipids together with the generation of hydroperoxide breakdown products were done with the use of the thiobarbituric acid test. The results of these experiments showed that the effectiveness of a given fatty acid in killing cancer cells correlated with the intracellular thiobarbituric acid-reactive material (TBARM) content: GLA and arachidonate with 3 and 4 double bonds generated the most TBARM and were the most cytotoxic fatty acids, whereas docosahexaenoate with 6 double bonds was the least effective either in raising TBARM or in killing the malignant cells. Iron and copper accelerated the rate of cell death, whereas antioxidants such as vitamin E and butylated hydroxyanisole inhibited the effect of GLA dose dependently. Indomethacin, an inhibitor of endoperoxide formation, did not reduce either cell kill or TBARM amounts. In contrast, the addition of vitamin E acetate to the cancer cell cultures challenged with eicosapentaenoate reduced both cell killing and TBARM content. These results suggest that the effectiveness of a given fatty acid in killing cancer cells correlated with the extent of lipid peroxidation of the added fatty acid in the cells.

Antioxidants↗
PubMed1988

Linoleic acid-induced fatty acid changes in platelet and aorta of the rat: effect of age and cholesterol.

The influence of age and cholesterol on polyunsaturated fatty acids (PUFA) levels was studied in young and old male Sprague-Dawley rats. Animals were fed a fat-free diet supplemented with 10% (by wt) safflower oil with or without 1% cholesterol for 8 wk. As a result of cholesterol feeding, proportions of linoleic acid (18:2n-6) and dihomo-gamma-linolenic acid (20:3n-6) were increased and that of arachidonic acid (20:4n-6) was decreased in the liver and platelet phospholipids in 64-wk-old rats, suggesting inhibitory effects of cholesterol on 20:4n-6 synthesis from 18:2n-6. The prominent age-dependent effect on the levels of PUFA was a retention of C-22 n-3 PUFA, accompanied by decreased C-22 n-6 PUFA and increased 20:3n-6 in the liver and platelet phospholipids. Ratio of 20:3n-6/20:4n-6 increased in 64-wk-old rats regardless of dietary cholesterol, suggesting depressed delta 5-desaturase with age. In aorta phospholipids, 20:3n-6 content and 20:3n-6/20:4n-6 ratio increased with cholesterol supplementation, but not with age. These results suggest that changes of PUFA composition of platelet phospholipids with age are closely linked with changes in liver phospholipids. The 20:4n-6 content in both platelet and aorta phospholipids is kept constant, despite other n-6 and n-3 PUFA being affected by age.

Adipose Tissue↗
PubMed1988

Effects of low magnesium diet on the vascular prostaglandin and fatty acid metabolism in rats.

Deficiency of magnesium with cardiovascular effects is thought to be related to alterations in the biosynthesis of prostaglandins (PGs) in the vasculature. Measurements were made of the PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) outflow from the perfused isolated mesenteric arterial bed and the fatty acid composition of the tissue in rats maintained for 14 weeks on a low magnesium (LMg) diet. The serum Mg levels were significantly decreased and the serum Ca levels were significantly increased in the LMg group as compared to the controls. The arachidonic acid concentration in the triacylglyceride fraction was significantly increased in the LMg group. Long chain polyunsaturates such as 22:4n6 and 22:6n3 were consistently increased in the LMg rats as compared to the controls in both the phospholipid and triglyceride fractions as previously reported in other tissues. The PGE2, 6-keto-PGF1 alpha and TxB2 outflows were significantly increased in the LMg group as compared to the controls. These findings suggest that the biosynthesis of eicosanoids, mainly PGI2, is stimulated in Mg deficiency, and this may provide protection against intracellular Mg depletion and Ca accumulation, so as to counteract to the constricted and hyperreactive state of the vasculature in such a condition.

Animals↗
PubMed1988

Effects of calcium deprivation on n-6 fatty acid metabolism in growing rats.

Two separate experiments examining the effects of calcium deficiency on plasma and liver fatty acids in rats were conducted. In Experiment I, weanling male Sprague-Dawley rats were fed a calcium-deficient diet with or without the supplementation of 5 or 20 g/kg calcium for 22 days. There were no significant differences in plasma and liver fatty acid distribution between the two calcium-supplemented groups. However, calcium deficiency significantly elevated the levels of 18:3n-6 in plasma and liver cholesteryl esters and liver phospholipids, while it reduced the levels of 20:3n-6 in plasma cholesteryl esters. In Experiment II, weanling rats were fed a calcium-deficient diet supplemented with 5 g/kg calcium for 22 days. After overnight fast, animals were given by intragastric feeding a dose of 4 g/kg body wt gamma-linolenic acid concentrate (containing 92% 18:3n-6 ethyl ester), and were killed 22 hr later. The levels of 18:3n-6 were significantly higher, whereas the levels of 20:3n-6 were either not changed or lower than those in calcium-supplemented group. In both experiments, the ratios of (20:3n-6 + 20:4n-6)/18:3n-6 in plasma and liver lipids were significantly reduced in calcium-deficient rats. These results suggest that calcium may play an important and specific role in the process of elongation of 18:3n-6 to 20:3n-6.

Aging↗