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PubMed1976

Essential fatty acids and fetal brain growth.

The fetal brain accumulates long-chain (C20 and 22) polyunsaturated fatty acids--arachidonic and docosahexaenoic--during cell division. De-novo synthesis of these acids does not occur and they are thought to be either directly derived from food or by metabolism from linoleic and linolenic acids, respectively. Administration of isotopically labelled linoleic and linolenic acids to pregnant guineapigs showed that only a small proportion of the label was converted to their respective long-chain polyunsaturated derivatives in the maternal liver. The proportion was increased within the phospholipids (structural lipids) by what appeared to be amultiple processing system which increased chain length and degree of polyunsaturation from maternal liver to placenta, fetal liver, and to fetal brain. Observations in man suggest a similar trend. The porportion of long-chain polyunsaturated acids increased in the phospholipids from maternal blood, cord blood, fetal liver, and fetal brain. These data show that the placenta and fetus are radically modifying the maternal phospholipids so as to achieve the high proportions of the C20 and C22 polyunsaturated fatty acids in the structural lipids of the developing brain.

Animals↗
PubMedDate not supplied

The role of the placenta in the supply of essential fatty acids to the fetal sheep: studies of lipid compositions at term.

A study has been made of the comparative distribution and fatty acid compositions of the major lipid fractions of maternal plasma, placenta and fetal plasma of the sheep at approximately 120 days of gestation. Cholesteryl esters and phospholipids constituted the major lipid fractions present in both maternal and fetal plasmas. In the placenta, phospholipids accounted for some 60 per cent of the total lipid present. Within the phospholipids of the maternal and fetal plasmas and placenta, phosphatidylcholine comprised the largest component. Whereas maternal plasma contained high levels of linoleic and arachidonic acids, fetal plasma contained a low proportion only a linoleic acid and high proportions of delta 5,8,11 eicosatrienoic acid and arachidonic acid. In the maternal plasma the arachidonic acid:linoleic acid ratio was only 0.17, but in the fetal plasma the ratio was 3.32. The differences in the lipid and fatty acid compositions between the maternal plasma, fetal plasma and placenta are discussed in relationship to the distinctive polyunsaturated fatty acid metabolism of the fetal and newborn lamb.

Animals↗
PubMed1998

Nitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/neuropathy--preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifylline.

Impaired microcirculatory perfusion appears to be crucial to the pathogenesis of both neuropathy and retinopathy in diabetics. This in turn reflects a hyperglycemically mediated perturbation of vascular endothelial function that entails overactivation of protein kinase C, reduced availability of nitric oxide, increased production of superoxide and endothelin, impaired insulin function, diminished synthesis of prostacyclin/PGE1, and increased activation and endothelial adherence of leukocytes. These dysfunctions may be addressed with a supplementation program that includes high-dose antioxidants, fish oil, gamma-linolenic acid, chromium, arginine, carnitine, and ginkgolides. Pharmaceuticals likely to be of benefit in this regard include pentoxifylline, probucol, replacement estrogens, and inhibitors of angiotensin converting enzyme and aldose reductase.

Animals↗
PubMed1997

Supplementation of MCF-7 cells with essential fatty acids induces the activation of protein kinase C in response to IGF-1.

The effects of changing the composition of membrane lipids on protein kinase C (PKC) activation were studied in MCF-7 human breast cancer cells. The supply of linoleate or alpha-linolenate to MCF-7 cells altered cell membranes fatty acid composition but did not affect PKC activity. When the cells were additionally exposed to IGF-1, the same fatty acids caused a dramatic increase in membrane-bound PKC activity. We also found that the mitogenic response induced by IGF-1 was not enhanced in those conditions when PKC becomes activated by linoleate and alpha-linolenate. These data show that these fatty acids elicit a distinct route for the transmission of IGF-1 signal by inducing the PKC pathway. They suggest that linoleate and alpha-linolenate could control the biological response of MCF-7 cells to IGF-1.

Breast Neoplasms↗
PubMed2003

Effects of essential fatty acids on mediators of mast cells in culture.

The objective of this study was to investigate the effects of alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) on the fatty acid composition and the activity and release of mast cell mediators in the canine mastocytoma cell line C2. Cells were cultured in Dulbecco's modified Eagle's medium mixed with 50% Ham's F12 (containing linoleic acid 0.14 micro M). The basic medium (DEH) was supplemented with 0.14 micro M alpha-linolenic acid. 14.0 micro M alpha-linolenic acid (DEH-n-3) or 14.0 micro M linoleic acid (DEH-n-6) was added. Eight days after culturing of C2 in DEH-n-3 we measured elevated levels of n-3 fatty acids up to 22:3. The tryptase activity and the stimulated PGE2 production and histamine release were reduced. In contrast, after culturing of C2 in DEH-n-6 we determined elevated levels of n-6 fatty acids up to 20:3, increased tryptase activity and stimulated histamine release. Thus 18:3n-3 has anti-inflammatory effects in cultured canine mastocytoma cells.

Animals↗
PubMed1996

Essential fatty acids and abnormal involuntary movements in the general male population: a study of men born in 1933.

Spontaneous and tardive dyskinesias were studied in a random population sample of 446 men, aged 59 years. Dyskinesia, defined as an AIMS score of at least 2 in any body part, was seen in 15.1% (n = 74). Dyskinetic men had a higher cigarette consumption, and they had higher frequencies of psychiatric morbidity and exposure to neuroleptics. Dyskinesia was also associated with several abnormalities in EFA concentrations in plasma, but the most consistent finding was the low arachidonic acid levels in phospholipids, triglycerides and cholesterol esters. In a logistic regression model, cigarette consumption (P < 0.02), exposure to neuroleptics (P < 0.01), and low arachidonic acid levels in the phospholipid fraction (P < 0.0001) were independently associated with dyskinesia.

Antipsychotic Agents↗
PubMed1997

Oxidant stress, anti-oxidants and essential fatty acids in systemic lupus erythematosus.

Eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA respectively) can suppress the production of interleukin-1 (IL-1), IL-2 and TNF (tumor necrosis factor) but not of IL-4 by human lymphocytes in vitro. In addition, the concentrations of EPA and DHA were also found to be low in the plasma phospholipid fraction of patients with SLE. In a limited clinical study performed by us earlier, it was observed that oral supplementation of EPA/DHA to patients with SLE can induce clinical remission without any side-effects. Since oxygen free radicals are known to be involved in the pathobiology of SLE, we estimated the plasma concentrations of lipid peroxides, nitric oxide, and anti-oxidants such as catalase, superoxide dismutase (SOD), glutathione peroxidase and vitamin E in these patients both before and after the induction of remission following EPA/DHA administration. These results showed that the levels of lipid peroxides are elevated and those of nitric oxide, SOD and glutathione peroxidase are decreased in SLE prior to EPA/DHA supplementation. Following EPA/DHA administration the concentrations of lipid peroxides, and those of nitric oxide, SOD and glutathione peroxidase reverted to near normal levels. These results suggest that oxidant stress, nitric oxide, and anti-oxidants play a significant role in SLE and that EPA/DHA can modulate oxidant stress and nitric oxide synthesis and may have a regulator role in the synthesis of anti-oxidant enzymes such as SOD and glutathione peroxidase. From the results of this study, we would like to suggest that measurement of lipid peroxides, nitric oxide and anti-oxidants can be used as markers to predict prognosis in patients with SLE.

Antioxidants↗
PubMed1998

Oxidant stress, anti-oxidants, nitric oxide and essential fatty acids in peptic ulcer disease.

In patients with duodenal ulcer (DU), the plasma levels of nitrite and lipid peroxides, the anti-oxidant content of red cells and plasma phospholipid fatty acid analysis were performed both before and after healing of the ulcer following treatment with lansoprazole, a proton pump inhibitor. These results showed that during the phase of active DU, the concentrations of antioxidants (superoxide dismutase, SOD, catalase and glutathione peroxidase) in red cells were low where as those of lipid peroxides and nitric oxide were high. Of the fatty acids measured, the concentration of palmitic acid (16:0) was increased during the active ulcer phase whereas those of arachidonic acid, alpha-linolenic acid and docosahexaenoic acid were low. These biochemical abnormalities reverted to normal following healing of the ulcer with lansoprazole. These results coupled with the observation that polyunsaturated fatty acids (PUFAs) can inhibit the growth of Helicobacterpylori and heal the ulcer suggest that free radicals, anti-oxidants, nitric oxide and PUFAs may play a significant role in the pathogenesis of DU. If this is true, it suggests that PUFAs can be exploited as potential anti-peptic ulcer drugs.

Adolescent↗