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Mechanisms of the selective cytotoxic actions of certain essential fatty acids.

Polyunsaturated fatty acids (PUFA) have a selective cytotoxic/cytostatic effect on a number of tumor cell lines in culture. Although this process may be enhanced by the addition of iron there is a minimum level of PUFA necessary for potentiation of cell death. Vitamin E blocks PUFA cytotoxicity when added up to 5 days after fatty acid administration. Levels of thio-barbiturate reactive material (TBARM) in the medium rise in parallel with cell death. However, they are not affected by small alterations in temperature or oxygen tension. Incubating cells with PUFA causes marked alterations in the fatty acid patterns of both neutral and phospholipid fractions. Membrane fluidity is increased and the activity of membrane-bound receptors may be influenced directly or through the actions of eicosanoids derived from the exogenous fatty acid. PUFA may be an effective way of influencing tumor growth and a safe approach for the management of human cancer.

Animals↗

Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin-diabetic rats; comparison with essential fatty acids.

In Study 1, the effects of treatment of streptozotocin-diabetic rats with the antioxidants, probucol or vitamin E were compared. Untreated diabetic rats showed a reduction of 45% (p < 0.01) in nerve laser Doppler flux, which was used as an index of nerve blood flow. In diabetic rats treated with either probucol or vitamin E nerve Doppler flux was reduced by only 13 or 16%, respectively (p < 0.01 for either compared to untreated diabetic rats). A second study examined the effects of treatment with evening primrose oil either alone or in combination with probucol. Reduced nerve Doppler flux was reproduced in untreated diabetic rats (47%; p < 0.01). In parallel diabetic groups, nerve Doppler flux was reduced by only 14% with evening primrose oil alone and by 8% with evening primrose oil plus probucol (both p < 0.01 vs untreated diabetic rats). Both treatments were also associated with marked attenuation of motor and sensory nerve conduction velocity deficits. Measurements on plasma from rats showed normalisation of triglyceride levels by probucol treatment without an effect on those of cholesterol in Study 1. In Study 2, the converse was true for evening primrose oil treatment, whilst the combined treatment lowered both plasma triglycerides and cholesterol. This work indicates similar effects of antioxidants and evening primrose oil against reduced nerve Doppler flux and conduction velocity in diabetic rats, with dissimilar actions on plasma triglycerides and cholesterol.

Animals↗

Essential fatty acid treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus.

In rats with 6 weeks streptozotocin-diabetes there was a 53% reduction in sciatic nerve laser Doppler flux compared to controls (p < 0.01). Treatment of a parallel group of diabetic rats with evening primrose oil, by dietary admixture throughout the protocol, prevented this ischaemia (Doppler flux was 91% of evening primrose-oil-treated controls and was not significantly different). There were no differences in systemic arterial pressure. In another experiment evening primrose oil markedly antagonised the development of exaggerated resistance to anoxic conduction failure in sciatic nerves from diabetic rats. The resistance to anoxia of nerves from non-diabetic rats was also reduced by evening primrose oil. These observations suggest that the sciatic nerves of diabetic rats with short-term streptozotocin-diabetes are markedly ischaemic and that this ischaemia is involved in the development of increased resistance to anoxic/ischaemic conduction failure in diabetic nerve. The findings also promote evening primrose oil as a potential treatment to prevent nerve ischaemia.

Animals↗

Relationships between essential fatty acid levels, pulmonary function and fat absorption in pre-adolescent cystic fibrosis children with good clinical scores.

Twenty-one pre-adolescent cystic fibrosis (CF) children with good clinical scores had significant (P less than 0.001) deficiencies of arachidonic (mean 3.8% of total plasma fatty acids +/- SD 1.4) and linoleic (18.1 +/- 6.3) acids compared with controls (6.0 +/- 1.0, and 27.6 +/- 3.9, respectively). Despite the presence of pulmonary involvement of varying severity in all the CF children, neither arachidonic nor linoleic acid levels correlated significantly with pulmonary function measured by spirometry. All children had adequate caloric and fat intakes, and the coefficient of fat absorption correlated with none of the deficient fatty acid levels. These findings suggest that deficiencies of arachidonic and linoleic acids are of minor importance in the early development of pulmonary involvement in CF, and that factors other than fat malabsorption and decreased dietary intake probably contribute to fatty acid deficiency.

Child↗

Pyelonephritis: renal urokinase activity in rats on essential fatty acid diets.

This study was undertaken to assess whether additions of different oils to the diets of male rats would affect the renal urokinase (UK) activity of healthy and pyelonephritic kidneys. Four groups of fatty acid diets were studied: fat-free, coconut oil, fish oil and evening primrose oil (EPO). Pyelonephritis was obtained by unilateral extrarenal urinary obstruction and subcutaneous injection of Escherichia coli. The UK activity of the non-obstructed kidneys did not differ statistically between rats infected and not infected with bacteria (P > 0.056), except within the coconut oil group. A statistically decreased UK activity was obtained with bacteria injected animals on a coconut oil diet (P < 0.0001). This phenomenon, namely a decrease in UK activity, was also seen with pyelonephritic kidneys of rats on fat-free, coconut and fish oil diets (P < 0.0065). However, the UK activity of the obstructed kidneys with and without infection in the EPO group remained similar (P = 0.8477). These results suggest that the UK activity in infection-induced renal stones may be restored by EPO containing diets and may be of high relevance in the prevention and treatment of infection-induced renal stones. This revelation now needs to be more fully investigated.

Animals↗

[Essential fatty acids in the plasma of severely injured patients under parenteral feeding].

After a heavy injury there are characteristic changes of plasma lipids and lipoproteins. In 7 patients up to 40 days after major injury the fatty acids of cholesteryl esters, phospholipids and triglycerides in plasma under the influence of injury, parenteral nutrition with carbohydrates or fat, and protein-sparing therapy were determined by gas liquid chromatography. These patients' increased requirement for linoleic acid is further increased by up to more than 50 g per day by carbohydrate-rich parenteral nutrition, inhibiting lypolysis of linoleic acid from adipose tissue. Protein-sparing therapy without carbohydrates is not sufficient to cover the patients' increased requirement for linoleic acid. Thus, the early administration of fat emulsions in parenteral nutrition is recommended.

8,11,14-Eicosatrienoic Acid↗

Essential fatty acids (EFA) deficiency and liver mitochondria.

2 dietary fats, namely, hydrogenated coconut oil and safflower seed oil were fed at 20% levels to weanling male albino rats for a period of 2 months after which the animals were sacrificed and oxidative phosphorylation measured in liver mitochondria. This ratio was more in the unsaturated-fat-fed group of rats compared to the saturated-fed ones for glutamate and malate; in the case of succinate no such change was noticed.

Animals↗

Relationship between dietary supply of long-chain fatty acids and membrane composition of long- and very long chain essential fatty acids in developing rat photoreceptors.

The present study was designed to determine if dietary supply of long-chain fatty acid (LCFA, C20:4n-6, and/or C22:6n-3), reflecting levels that might be incorporated into infant formulas, influences the fatty acid composition of the visual cell membrane. The rod outer segment (ROS) of the retina was analyzed from rats fed diets varying in the ratio of 18:2n-6 to 18:3n-3 with or without 20:4n-6 [arachidonic acid (AA)] and 22:6n-3 (docosahexaenoic acid) from birth to six weeks of age. The level of very long chain fatty acids (VLCFA, C24-C36) was identified using gas chromatography and gas chromatography-mass spectrometry. In the ROS, the highest relative percent of AA was attained in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of animals fed 1% AA diet, whereas feeding 0.7% docosahexaenoic acid (DHA) diet significantly increased the DHA level in PC, phosphatidylserine, and phosphatidylinositol compared to feeding diets containing AA. VLCFA of n-6 and n-3 up to C36 were found in PC, with the most abundant fatty acids being C32 and C34. In PC, phosphatidylserine and PE, the n-6 tetraenoic VLCFA level was highly increased in animals fed 1% AA compared to other dietary groups. This study suggests that dietary fat containing small amounts of AA or DHA is an important factor influencing membrane fatty acid composition of the visual cell during development.

Animals↗