γ-Linolenic acid: Purification and functionality

Handbook of Functional Lipids

Volumn , Issue , 2005, Pages 47-75

  Wanasundara, Udaya N ^a   Wanasundara, Janitha P D ^b  

^a POS Pilot Plant Corporation   (Canada)

^b AGRICULTURE AND AGRI FOOD CANADA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84940104189     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (189)

1. Heiduschka, A. and Lueft, K., Fatty oil from the seed of the evening primrose (Oenothera biennis) and a new linolenic acid, Arch. Pharm., 257, 33, 1919.
2. Eibner, A. and Schild, E., Quantitative analysis and technical evaluation of a Oenothera oil, Chem. Umschau Fette, Oele, Wachse Harze, 34, 339, 1927.
3. Riley, J.P., Seed fat of Oenothera biennis L., J. Chem. Soc., 4, 2728, 1949.
4. Wolf, R.B., Kleiman, R., and England, R.E., New sources of γ-linolenic acid, J. Am. Oil Chem. Soc., 60, 1858, 1983.
5. Gunstone, F.D., Gamma linolenic acid: occurrence and physical and chemical properties, Prog. Lipid Res., 31, 145, 1992.
6. Guil-Guerrero, J.L. et al., Occurrence and characterization of oils rich in γ-linolenic acid Part I: Echium seeds from Macaronesia, Phytochemistry, 53, 451, 2000.
7. Guil-Guerrero, J.L. et al., γ-Linolenic acid from fourteen Boraginaceae species, Ind. Crops Prod., 18, 85, 2003.
8. Goffman, F.D. and Galletti, S., Gamma-linolenic acid and tocopherol contents in the seed oil of 4 accessions from several Ribes species, J. Agric. Food Chem., 49, 349, 2001.
9. Traitler, H. et al., Characterization of γ-linolenic acid in Ribes seed, Lipids, 19, 923, 1984.
10. Ucciani, E., Sources potentielles d'acide gamma-linolenique:une revue, OC, 2, 319, 1995.
11. Oomah, D.B. et al., Characteristics of hemp (Cannabis sativa L.) seed oil, Food Chem., 76, 33, 2002.
12. Ratledge, C., Microbial oils and fats: an assessment of their commercial potential, Prog. Ind. Microbiol., 16, 119, 1982.
13. Komisaka, Y. et al., Modulation of fatty acid incorporation and destauration by Trifluoperazine in fungi, Lipids, 25, 787, 1990.
14. Aggelis, G. et al., Possibility of gamma-linolenic acid production by culturing Mucor circinelloides CBS 172-27 on some vegetable oils, Oleagineux, 41, 208, 1991.
15. Aggelis, G. et al., Gamma-linolenic acid production by bioconversion of the linoleic acid of some oils, Rev. Fr. Crops Gras, 38, 95,1991.
16. Miura, Y. et al., Production of γ-linolenic acid from marine green alga Chlorella sp. NKG 042401, FEMS Microbiol. Lett, 107, 163, 1993.
17. Srinivas, C.V.S., Praveena, B., and Nagaraj, G., Safflower petals: a source of gamma linolenic acid, Plant Foods Human Nutr., 54, 89, 1999.
18. Stymme, S. and Stobart, A.K., Biosynthesis of γ-Linolenic acid in cotyledons and microsomal preparations from the developing seeds of common borage (Borago officinalis), Biochem. J., 240, 385, 1986.
19. Griffith, G., Stobart, A.K., and Stymme, S., Δ6- and Δ12-Desaturase activities and phosphatidic acid formation in microsomal preparations from developing cotyledons of common borage (Borago officinalis), Biochem. J., 252, 641, 1988.
20. Galle, A.M. et al., Biosynthesis of γ-linolenic acid in developing seeds of borage (Borago officinalis L.), Biochim. Biophys. Acta, 1158, 52, 1993.
21. Talamo, B., Chang, N., and Bloch, K., Desaturation of oleyl phospholipid to linoleyl phospholipid in Torulopsis utilis, J. Biol. Chem., 248, 2738, 1973.
22. Pugh, E.L. and Kates, M., Desaturation of phosphatidylcholine and phosphatidyle-thanolamine by a microsomal enzyme from Candida lipolytica, Biochim. Biophys. Acta, 316, 305, 1973.
23. Pugh, E.L. and Kates, M., Characterization of a membrane bound phospholipid desaturase system of Candida lipolytica, Biochim. Biophys. Acta, 380, 442, 1975.
24. Sato, N., Seyama, Y., and Murata, N., Lipid linked desaturation of palmitic acid in monogalactosyl diacylglycerol in the blue-green algae (Cynobacterium) Anabaena variabilis studied in vivo, Plant Cell Physiol., 27, 819, 1986.
25. Murata, N., Deshnium, P., and Tasaka, Y., Biosynthesis of γ-linolenic acid in the Cyanobacterium Spirulina platensis, in γ-Linolenic acid: Metabolism and Its Roles in Nutrition and Medicine, Huang, Y.-S. and Mills, D.E., Eds., AOCS Press, Champaign, IL1996, p. 22.
26. Huang, Y.-S. et al., Cloning of Δ12-and Δ6-desaturases from Mortiella alpina and recombinant production of γ-linolenic acid Saccharomyces cerevisiae, Lipids, 34, 649, 1991.
27. Sakuradani, E. et al., Δ6-Fatty acid desaturase from an arachidonic acid-producing Mortierella fungus gene cloning and its heterologous expression in a fungus, Aspergillus, Gene, 238, 445, 1999.
28. Mukerji, P. et al., Desaturase genes and uses thereof., U.S. Patent 6,635,451 B2, 2003.
29. Reddy, A.S. and Thomas, T.L., Expression of a cyanobacterial Δ6-desaturase gene results in gamma-linolenic acid production in transgenic plants, Nat. Biotechnol., 14, 639, 1996.
30. Thomas, T.L., Production of gamma linolenic acid by a Δ6-desaturase, U.S. Patent 6,355,861 B1, 2002.
31. Knutzon, D., Polyunsaturated fatty acids in plants, U.S. Patent 6,459,018 B1, 2002.
32. Horrobin, D.F., Nrutitional and medical importance of gamma-linolenic acid, Prog. Lipid Res., 31, 163, 1992.
33. Phillips, J.C. and Huang, Y.S., Natural sources and biosynthesis of γ-linolenic acid: an overview, in γ-Linolenic Acid: Metabolism and Its Roles in Nutrition and Medicine, Huang, Y.-S. and Mills, D.E., Eds., AOCS Press, Champaign, IL, 1996, p. 1.
34. Mead, J.F., Synthesis and metabolism of polyunsaturated acids, Fed. Proc., 20, 952, 1961.
35. Okayasu, T. et al., Purification and partial characterization of linoleoyl-CoA desaturase from rat liver microsomes, Arch. Biochem. Biophys., 206, 21, 1981.
36. Thomasson, H.J., Stearolic acid, an essential fatty acid?, Nature, 173, 452, 1954.
37. Rivers, J.P.W. and Frankel, T.L., Essential fatty acid deficiency, Br. Med. Bull. 37, 59, 1981.
38. Horrobin, D.F., Gamma-linolenic acid, Rev. Contemp. Physiol., 1, 1, 1990.
39. Helme, J.P., Evening primrose, borage and blackcurrant seeds, in Oils and Fats Manual Vol. I, Karleskind, A., Ed., Intercept Ltd., 1996, p. 168.
40. Gawdzik, J. et al., Supercritical fluid extraction of oil from evening primrose (Oenothera paradoxa H.) seeds, Chem. Anal. 43, 695, 1998.
41. Gomez, A.M. and dela Ossa, E.M., Quality of borage seed oil extracted by liquid and supercritical carbon dioxide, Chem. Eng. J., 88, 103, 2002.
42. 2 and its mixture with caprylic acid methyl ester, J. Supercrit. Fluids, 22, 211, 2002.
43. Ratnayake, W.M.N., Matthews, D.G., and Ackman, R.G., Triacylglycerols of evening primrose (Oenothera biennis) seed oil, J. Am. Oil Chem. Soc., 66, 966, 1989.
44. Christie, W.W., Fractionation of the triacylglycerols of evening primrose oil by highperformance liquid chromatography in silver ion mode, Fat Sci. Technol., 93, 65, 1993.
45. Tsevegsuren, N. and Aitzetmuller, K., γ-Linolenic acid in anemone spp. seed lipids, Lipids, 28, 841, 1993.
46. Perrin, J.-L. et al., Analysis of triglyceride species of blackcurrant seed oil by HPLC via a laser light scattering detector, Rev. Fr. Crops Gras, 34, 221, 1987.
47. Aitzetmuller, K. and Gronheim, M., Separation of highly unsaturated triacylglycerols by reversed phase HPLC with short wavelength UV detection, J. High Resol. Chromatogr., 15, 219, 1992.
48. Blomberg, L.G., Bemirbuker, M., and Andersson, P.E., Argentation supercritical fluid chromatography for quantitative analysis of triacylglycerols, J. Am. Oil Chem. Soc., 70, 939, 1993.
49. Manninen, P., Laakso, P., and Kallio, H., Separation of γ- and A-linolenic acid containing triacylglycerols by capillary supercritical fluid chromatography, Lipids, 30, 665, 1995.
50. Redden, P.R. et al., Stereospecific analysis of the major triacylglycerol species containing γ-linolenic acid in evening primrose oil and borage oil, J. Chromatogr. A, 704, 99, 1995.
51. Lawson, L.D. and Hughes, G.B., Triacylglycerol structure of plant and fungal oils containing γ-linolenic acid, Lipids, 23, 313, 1988.
52. Griffiths, G., Stobat, A.K., and Stymne, S., The Δ6- and Δ12-desaturase activities and phosphatidic acid formation in microsomal preparations from the developing cotyledons of common borage (Borago officinalis), Biochem. J., 252, 641, 1988.
53. Laakso, P. and Christie, W.W., Chromatographic resolution of chiral diacylglycerol derivatives: potential in the stereospecific analysis of triacyl-sn-glycerols, Lipids, 25, 349, 1990.
54. Shimada, Y., Sugihara, A., and Tominaga, Y., Enzymatic purification of polyunsaturated fatty acids: a review, J. Biosci. Bioeng., 91, 529, 2001.
55. Chen, T.-C. and Ju, Y.-H., Polyunsaturated fatty acid concentrates from borage and linseed oil fatty acids, J. Am. Oil Chem. Soc., 78, 485, 2001.
56. Constantin, B. et al., Concentrate of polyunsaturated fatty acid ethyl esters and preparation thereof, U.S. Patent US 5,679,809, 1997.
57. Traitler, H., A process for enrichment with delta-6 fatty acids of a mixture of fatty acids, U.S. Patent 4,776,984, 1988.
58. Abril, J.R., Banzhaf, W., and Kohn, G., Production of human, animal or aquaculture organism diet supplement enriched with gamma linolenic acid and stearidonic acid by producing polar lipid rich fraction from plant seeds and microbes, International Patent, WO 200,292,073, 2003.
59. Wanasundara U.N. and Fedec, P., Centrifugal partition chromatography (CPC): emerging separation and purification technique for lipid related compounds, Inform, 13, 726, 2002.
60. Shimada, Y. et al., Purification of γ-linolenic acid from borage oil a two-step enzymatic method: hydrolysis and selective esterification, J. Am. Oil Chem. Soc., 74, 1465, 1997.
61. Shimada, Y. et al., Large scale purification of γ-linolenic acid by selective esterification using Rhizopus delemar lipase, J. Am. Oil Chem. Soc., 75, 1539, 1998.
62. Fan, Y.-Y. and Chapkin, R.S., Importance of dietary γ-linolenic acid in human health and nutrition, J. Nutr, 128, 1411, 1998.
63. 1 synthesis is altered by dietary γ-linolenic acid, J. Nutr., 122, 1600, 1992.
64. Jowett, P., 1-Mono-glyceride esters of gamma-linolenic acid, G.B. Patent 2 183 635 A, 1986.
65. Kawashima, A. et al., Production of structured TAG rich in 1,3-diacapryloyl-2-γ-linolenoyl glycerol from borage oil, J. Am. Oil Chem. Soc., 79, 871, 2002.
66. Akoh, C.C. and Moussata, C.O., Lipase-catalyzed modification of borage oil: incorporation of capric and eicosapentaenoic acids to form structured lipids, J. Am. Oil Chem. Soc., 75, 697, 1998.
67. Senanayake, S.P.J.N. and Shahidi, F., Enzyme-assisted acidolysis of borage (Borago officinalis L.) and evening primrose (Oenothera biennis L.) oils: incorporation of omega-3 polyunsaturated fatty acids, J. Agric. Food Chem., 47, 3105, 1999.
68. Senanayake, S.P.J.N. and Shahidi, F., Structured lipid via lipase-catalyzed incorpo-ratin of eicosapentaenoic acid to borage (Borago officinalis L.) and evening primrose (Oenothera biennis L.) oils, J. Agric. Food Chem., 50, 477, 2002.
69. Chapkin, R.S., Reappraisal of essential fatty acids, in Fatty Acids in Food and Their Health Implications, 2nd ed., Chow, C.K., Ed., Marcel Dekker, New York, 2000, p. 557.
70. Warrington, J.R., Interleukin-2 abnormalities in systemic lupus erythematosus and rheumatoid arthritis: a role for overproduction of interleukin-2 in human autoimmunity, J. Rheumatol., 15, 616, 1988.
71. Willis, A.L., Nutritional and pharmacological factors in eicosanoid biology, Nutr. Rev., 39, 289, 1981.
72. Zurier, R.B. et al., Gamma-linolenic acid treatment of rheumatoid artheritis: a randomized, placebo-controlled trial, Arthritis Rheum., 39, 1808, 1996.
73. Johnson, M.M. et al., Dietary supplementation of γ-linolenic acid alters fatty acid content and eicosanoid production of healthy humans, J. Nutr., 127, 1435, 1997.
74. Borgeat, P., Hamberg, M., and Samuelsson, S., Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes to mono-hydroxy acids from novel lipoxygenase, J. Biol. Chem., 251, 7816, 1976.
75. Barre, D.E., Potential of evening primrose, borage, black currant, and fungal oils in human health, Ann. Nutr. Metab., 45, 47, 2001.
76. Fan, Y.-Y., Ramos, K.S., and Chapkins, R.S., Dietary γ-linolenic acid modulates macrophage-derived soluble factor that down regulates DNA synthesis in smooth muscle cells, Arterioscler. Thromb. Vasc. Biol., 15, 1397, 1995.
77. Chapkin, R.S. et al., Ability of monohydroxyeicosatrienoic acid (15-OH-20:3) to modulate macrophage arachidonic acid metabolism, Biochem. Biophys. Res. Commun., 153, 799, 1988.
78. Miller, C.C. et al., Dietary supplementation with ethyl ester concentrates of fish oil (n-3) and borage oil (n-6) polyunsaturated fatty acids induce epidermal generation of local putative anti-inflammatory metabolites, J. Invest. Dermatol, 96, 98, 1991.
79. Goulet, J.L. et al., Altered inflammatory responses in leukotriene-deficient mice, Proc. Natl. Acad. Sci. USA, 91, 12852, 1994.
80. Cho, Y. and Ziboh, V.A., A novel 15-hydroxyeicosatrienoic acid substituted diacylg-lycerol (15-HETrE-DAG) selectively inhibits epidermal protein kinase CB, Biochim. Biophys. Acta, 1349, 67, 1997.
81. Brenner, R.R., De Tomas, M.E., and Peluffa, R.O., Effect of polyunsaturated fatty acids on the desaturation in vitro of linoleic to γ-linolenic acid, Biochim. Biophys. Acta, 106, 640, 1965.
82. Manku, M.S. et al., Essential fatty acids in plasma phospholipids of patients with atopic eczema, Br. J. Dermatol., 110, 643, 1984.
83. Wu, D. and Meydani, S.N., γ-Linolenic acid and immune function, in γ-Linolenic Acid: Metabolism and Its Roles in Nutrition and Medicine, Huang, Y.-S. and Mills, D.E., Eds., AOAC Press, Champaign. IL, 1996, p. 106.
84. Tate, G. et al., Suppression of acute and chronic inflammation by dietary gamma linolenic acid, J. Rheumatol, 16, 729, 1989.
85. Nerad, J.L., Meydani, S.N., and Dinarello, C.A., Dietary supplementation with gamma linolenic acid (GLA) and parameters of cell-mediated immunity, Cytokine, 3, 513, 1991.
86. Fan, Y.-Y., and Chapkin, R.S., Mouse peritoneal macrophage prostaglandin E synthesis is altered by dietary γ-linolenic acid, J. Nutr., 122, 1600, 1996.
87. Goodwin, J.S. and Webb, D.R., Regulation of the immune response by prostaglandins, Clin. Immunol. Immunopathol., 15, 106, 1977.
88. Rappaport R.S. and Dodge, G.R., Prostaglandin E inhibits the production of human interleukin 2, J. Exp. Med., 155, 943, 1982.
89. Vassilopoulas, D. et al., Gamma linolenic acid and dihomo gamma linolenic acid suppress the CD3-mediated signal transduction pathway in human T cells, Clin. Immunol. Immunopathol., 83, 237, 1997.
90. Rossetti, R.G. et al., Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation, J. Leukotr. Biol., 62, 438, 1997.
91. Krakauer, K.A., Torrey, S.B., and Zurier, R.B., Prostaglandin! treatment of NZB/w mice III: preservation of spleen cell concentrations and mitogen induced proliferative responses, Clin. Immunol. Immunopathol., 11, 256, 1978.
92. Dore-Duffy, P., Siok, C., and Zurier, R.B., Oral administration of prostaglandin E to humans: effects on peripheral blood leukocyte function, J. Lab. Clin. Med., 104, 283, 1984.
93. Callegari, P.E. and Zurier, R.B., Botanical lipids: potential role in modulation of immunologic responses and inflammatory reactions, Nutr. Rheum. Dis., 17, 415, 1991.
94. Kunkel, S.L. et al., Suppression of chronic inflammation by evening primrose oil, Prog. Lipid Res., 20, 886, 1981.
95. Tate, G. et al., Suppression of monosodium urate crystal induced acute inflammation by diets enriched with gamma linolenic acid and eicosapentaenoic acid, Arthritis Rheum. 31, 1543, 1988.
96. Pullman-Moor, S. et al., Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid, Arthritis Rheum., 33, 1526, 1990.
97. Leventhal, L.J., Boyce, E.G, and Zurier, R.B., Treatment of rheumatoid arthritis with gamma linolenic acid, Ann. Intern. Med., 119, 867, 1993.
98. Zurier, R.B. et al., Gamma linolenic acid treatment of rheumatoid arthritis. A randomized placebo-controlled trial, Arthritis Rheum., 39, 1808, 1996.
99. Soeken, K.I., Miller, S.A., and Ernst, E., Herbal medicines for the treatment of rheumatoid arthritis: a systemic review, Rheumatology, 42, 652, 2003.
100. Burr, G.O. and Burr, M.M., A new deficiency disease produced by the rigid exclusion of fat from diet, J. Biol. Chem., 82, 3457, 1929.
101. Burr, G.O. and Burr, M.M., The nature and role of the fatty acids essential in nutrition, J. Biol. Chem., 86, 587, 1930.
102. Vorman, H.E., Nemeck, R.A., and Hsia, S.L., Synthesis of lipids from acetate by human preputial and abnormal skin in vitro, J. Lipid Res., 10, 507, 1969.
103. Ziboh, V.A., Biochemical abnormalities in essential fatty acid deficiency, Models Dermatol., 3, 106, 1987.
104. Ziboh, V.A., The significance of polyunsaturated fatty acids in cutaneous biology, Lipids, 31, 249, 1996.
105. Ziboh, V.A., Miller, C.C., and Cho, Y., Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of anti-inflammatory and antiproliferative metabolites, Am. J. Clin. Nutr, 7, 361S, 2000.
106. Miller, C.C. et al., Oxidative metabolism of dihomo-γ-linolenic acid by guinea pig epidermis: evidence of generation of anti-inflammatory products, Prostaglandins, 35, 917, 1988.
107. Lovell, C.R., Burton, J.L., and Horrobin, D.F., Treatment of atopic eczema with evening primrose oil, Lancet, 1, 278, 1981.
108. Wright, S. and Burton, J.L., Oral evening primrose-seed oil improves atopic eczema, Lancet, 99, 1120, 1982.
109. Manku, M.S. et al., Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy, Prostag. Leukotr. Med., 9, 615, 1982.
110. Horrobin, D.F., Essential fatty acid metabolism and its modification in atopic eczema, Am. J. Clin. Nutr., 7, 367S, 2000.
111. Ziboh, V.A., Implications of dietary oils and polyunsaturated fatty acids in the management of cutaneous disorders, Arch. Dermatol., 125, 241, 1989.
112. Chapkin, R.S., Fan, Y. -Y., and Ramos, K.S., Impact of dietary γ-linolenic acid on macrophage-smooth muscle cell interactions: down-regulation of vascular smooth muscle cell DNA synthesis, in γ-Linolenic Acid: Metabolism and Its Roles in Nutrition and Medicine, Huang, Y.-S. and Mills, D.E., Eds., AOCS Press, Champaign, IL, 1996, p. 218.
113. Sperling, R., The effects of dietary n-3 polyunsaturated fatty acids on neutrophils, Proc. Nutr. Soc., 57, 527, 1998.
114. Fan, Y.-Y., Ramos, K.S., and Chapkin, R.S., Modulation of atherogenesis by dietary gamma-linolenic acid, in Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4, Honn, K.V., Marnett, L.J., Nigam, S., and Dennis, E.A., Eds., Kluwer Academic/Plenum, New York, 1999, p. 485.
115. Negishi, M., Sugimoto, Y., and Ichikawa, A., Prostaglandin receptors and their biological actions, Prog. Lipid Res., 32, 417, 1993.
116. Foulkes, N.S. and Sasone-Corsi, P., Transcription factors coupled to the cAMP signalling pathway, Biochim. Biophys. Acta, 1288, F101, 1996.
117. 1: relationship to intra-cellular cAMP levels, Prostaglandins Leukotr. Essent. Fatty Acids, 54,101, 1996.
118. Fan Y.-Y., Ramos, K.S., and Chapkin, R.S., Dietary lipid source alters murine macrophage/vascular smooth muscle cell interactions in vitro, J. Nutr., 126, 2083, 1996.
119. 1 which inhibits vascular smooth muscle cell proliferation, J. Nutr., 127, 1765, 1997.
120. Fan Y.-Y., Ramos, K.S., and Chapkin, R.S., Dietary gamma-linolenic acid suppresses aortic smooth muscle cell proliferation and modifies atherosclerotic lesions in apo-lipoprotein E knockout mice, J. Nutr., 131, 1675, 2001.
121. Spector, A.A. and Yorek, M.A., Membrane lipid composition and cellular function, J. Lipid Res, 26, 1015, 1985.
122. Engler, M.M. et al., Effects of dietary γ-linolenic acid on blood pressure and adrenal angiotensin receptors in hypertensive rats, Proc. Soc. Exp. Biol. Med., 218, 234, 1998.
123. Goodfriend, T.L. et al., Fatty acids are potential regulators of aldosterone secretion, Endocrinology, 128, 2511, 1991.
124. Engler, M.M., γ-Linolenic acid: a potent blood pressure lowering nutrient, in γ-Linolenic Acid: Metabolism and Its Roles in Nutrition and Medicine, Huang, Y.-S. and Mills, D.E., Eds., AOCS Press, Champaign, IL, 1996, p. 200.
125. Leeds, A.R., Gray, I., and Ahmed, M., Effects of n-6 essential fatty acids as evening primrose oil in mild hypertension, in Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine, Horrobin, D.F., Ed., Alan Liss, New York, 1990, p. 56.
126. Deferne, J.-L. and Leeds, A.R., The antihypertensive effect of dietary supplementation with a 6-desaturated essential fatty acid concentrate as compared with sunflower seed oil, J. Human Hypertens., 6, 1, 1992.
127. Engler, M.M., Comparative study of diets enriched with evening primrose, blackcur-rent, borage, or fungal oils on blood pressure and pressor responses in spontaneously hypertensive rats, Prostaglandins Leukotr. Essent. Fatty Acids, 49, 809, 1993.
128. Takayasu, K. and Yoshikawa, I., The influence of exogenous cholesterol on the fatty acid composition of liver lipids in the rats given linoleate and γ-linolenate, Lipids, 6, 47, 1971.
129. 2, Med. Hypothesis, 6, 785, 1980.
130. Horrobin, D.F., The use of gamma-linolenic acid in diabetic neuropathy, Agents Action Suppl., 37, 120, 1992.
131. 1 on high-density lipoprotein-fraction lipid levels in rats, Biochem. Med. Metab. Biol., 36, 114, 1986.
132. 1 suppress sterol synthesis in freshly isolated human mononuclear leukocytes, Biochim. Biophys. Acta, 835, 157, 1985.
133. Krone, W., Betteridge, D.J., and Galton, D.J., Mechanism of regulation of 3-hydroxy-3-methylglutaryl coenzyme: a reductase activity by low-density lipoprotein in human lymphocytes, Eur. J. Clin. Invest., 9, 405, 1979.
134. Maziere, C., CyclicAMP decreases LDL catabolism and cholesterol synthesis in the human hepatoma cell line HepG2, Biochem. Biophys. Res. Commun., 156, 424, 1988.
135. Stout, R.W. and Bierman, E.L., Dibutyryl cyclicAMP inhibits LDL binding in cultured fibroblasts and arterial smooth muscle cells, Artherosclerosis, 46, 13, 1983.
136. Fox, J.C., et al., In vivo regulation of hepatic LDL receptor mRNA in the baboon: differential effects of saturated and unsaturated fat, J. Biol. Chem., 262, 7014, 1987.
137. Huang, Y.-S., Manku, M.S., and Horrobin, D.F., The effect of dietary cholesterol on blood and liver polyunsaturated fatty acid on plasma cholesterol in rats fed various types of fatty acid diet, Lipids, 19, 664, 1984.
138. Leary, W.P. et al., Some effect of gamma-linolenic acid on cultured human oesoph-ageal carcinoma cells, S. Afr. Med. J., 82, 681, 1984.
139. Begin, M.E. et al., Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids, J. Natl. Cancer Inst., 177, 1053, 1986.
140. Seigal, I. et al., Cytotoxic effects of free fatty acids on ascites tumor cells, J. Natl. Cancer Inst., 78, 271, 1987.
141. Das, U.N., Selective enhancement of free radicals in tumor cells as a strategy to kill tumor cells both in vitro and in vivo, in Biological Oxidation Systems, Reddy, C.C. et al., Eds., Academic Press, New York, 1990, p. 607.
142. Das, U.N., Essential fatty acids, lipid peroxidation and apoptosis, Prostaglandins Leukotr. Essent. Fatty Acids, 61, 157, 1999.
143. Das, U.N., Gamma-linolenic acid, arachidonic acid and eicosapentaenoic acid as potential anticancer drugs, Nutrition, 6, 419, 1990.
144. Cheeseman, K.H. et al., Studies on lipid peroxidation in normal and tumor tissues, Biochem. J., 250, 247, 1988.
145. Masotti, L., Cassali, E., and Galeotti, T., Lipid peroxidation in tumor cells, Free Radic. Biol. Med., 4, 377, 1988.
146. Gerber, M. et al., Relationship between vitamin E and polyunsaturated fatty acids in breast cancer: nutritional and metabolic aspects, Cancer Res., 64, 2347, 1989.
147. Tanaka, H. et al., The effect of PGD2 and 9-deoxy-9PGD2 on colony formation of murine osteosarcoma cells, Prostaglandins, 30, 167, 1985.
148. Sakai, T. et al., Prostaglandin D2 inhibits the proliferation of human malignant tumor cells, Prostaglandins, 27, 17, 1984.
149. Myers, R.L. and Siegal, M.I., The appearance of phospholipase activity in the human macrophage-like cell line U937 during dimethyl sulfoxide-induced differentiation, Biochem. Biophys. Res. Commun., 30, 167, 1984.
150. Bonser, R.W. et al., The appearance of phospholipase and cyclo-oxygenase activities in the human promyelocytic leukemia cell line HL-60 during bimethyl sulfoxide-induced differentiation, Biochem. Biophys. Res. Commun., 98, 614, 1981.
151. Dunbar, L.M. and Bailet, J.M., Enzyme deletion and essential fatty acid metabolism in cultured cells, J. Biol. Chem., 250, 1152, 1975.
152. Das, U.N., Devi, G.R., and Res, K.P., Benzo(a)pyrene and gamma-radiation induced genetic damage in mice can be prevented by gamma-linolenic acid but not by arachi-donic acid, Nutr. Res., 5, 101, 1985.
153. Renner, H.W. and Declincee, H., Different anti-mutagenic acitons of linoleic and linolenic acid derivatives on Busulfan-induced chromosomal damage to human lymphocytes in vitro, Nutr. Rep. Int., 36, 1276, 1987.
154. Das, U.N., Tumoricidal action of cis-unsaturated fatty acids and its relationship to free radicals and lipid peroxidation, Cancer Lett, 50, 235, 1991.
155. Eriksson, L. et al., Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogensis, Environ. Health Per-spect., 49, 171, 1983.
156. Faber, E., The biochemistry of generation of preneoplastic liver: a common metabolic pattern in hepatocyte nodules, Can. J. Biochem Cell Biol. 62, 486, 1984.
157. Sun, Y., Free radicals, antioxidant enzymes and carcinogenesis, Free Radic. Biol. Med., 8, 583, 1990.
158. Oberlcy, L.W. and Buettner, G.R., Role of superoxide dismutase in cancer: a review, Cancer Res, 39, 1141, 1979.
159. De Vries, C.E.E. and Van Noorden, C.J.F., Effects of fatty acid composition on tumor growth and metastatis, Anticancer Res., 12, 1513, 1992.
160. Slater, T.F., Free radicals and tissue injury: fact and fiction, Br. J. Cancer, 55, Suppl., 8, 5, 1987.
161. Slater, T.F. et al., Studies on the hyperplasia (regeneration) of the rat liver, following partial hepatectomy: changes in lipid peroxidation and general biochemical aspects, Biochem. J., 265, 51, 1990.
162. Calorini, L. et al., Lipid characteristics of RSV-transformed Balb/c 3T3 cell lines with different spontaneous metastatic potentials, Lipids, 24, 685, 1989.
163. Bennet, A., Prostanoids and cancer, Ann. Clin. Res., 16, 314, 1984.
164. Dragao, J.R., Rohner, T.J., and Demers, L.M., The synthesis of prostaglandins by the NB rat prostate tumor, Anticancer Res., 5, 393, 1985.
165. Fulton, A.M., Effects of indomethacine on the growth of cultured mammary tumors, Cancer Res., 44, 2416, 1984.
166. El-Ela, S.H.A. et al., Effects of dietary primrose oil on mammary tumorgenesis induced by 7,12-dimethyl benz(a)anthracene, Lipids, 22, 1041, 1987.
167. Cai, J., Jiang, W.G., and Mansel, R.E., Inhibition of angiogenic factor- and tumor-induced angiogenesis by gamma linolenic acid, Prostaglandins Leukotr. Essent. Fatty Acids, 60, 21, 1999.
168. Sangeetha, P.S. and Das, U.N., Gamma linolenic acid and eicospentaenoic acid potentiate the cytotoxicity of anti-cancer drugs on cervical carcinoma (HeLa) cells in vitro, Med. Sci. Res., 21, 457, 1993.
169. Vartak, S., Robbins, M.E., and Spector, A.A., Polyunsaturated fatty acids increase the sensitivity of 36B10 rat astrocytoma cells to radiation-induced cell kill, Lipids, 32, 283, 1997.
170. Das, U.N., Prakash, V.K.S., and Reddy, D.R., Local application of γ-linolenic acid in the treatment of human gliomas, Cancer Lett., 94, 147, 1995.
171. Bakashi, A. et al., γ-Linolenic acid therapy of human gliomas, Nutrition 19, 305, 2003.
172. Kenny, F.S. et al., Gamma linolenic acid with tamoxifen as primary therapy in breast cancer, Int. J. Cancer, 85, 643, 2000.
173. Menendez, J.A. et al., Effects of gamma linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells, Eur. J. Cancer, 31, 402, 2001.
174. Tilvis, R.S. and Miettinen, T.A., Fatty acid composition of serum lipids, erythrocytes and platelets in insulin dependant diabetic women, J. Clin. Endocrinol. Metab., 61, 741, 1985.
175. 2 and serum fatty acid levels, J. Pediatr. Gastroenterol. Nutr., 5, 878, 1986.
176. Mercuri, O., Peluffo, R.O., and Brenner, R.R., Depression of microsomal desaturation of linoleic to gamma-linolenic acid in the alloxan diabetic rat, Biochim. Biophys. Acta, 116, 409, 1966.
177. Poisson, J.P., Comparative in vivo and in vitro studies of the influence of experimental diabetes on rat liver linoleic acid delta-6- and delta-5-desaturation, Enzyme, 34, 1, 1985.
178. Morita, I. et al., Increased arachidonic acid content in platelet phospholipids from diabetic patients, Prostaglandins Leukotr. Med., 11, 33, 1983.
179. Takahashi, R., Morse, N., and Horrobin, D.F., Plasma, platelet and arota fatty acids composition in response to dietary n-6 and n-3 fats supplementation in a rat model of non-insulin dependant diabetes, J. Nutr. Sci. Vitaminol., 34, 413, 1988.
180. Van Doormaal, J.J., Idema, I.G., and Muskiet, F.A.J., Effects of short term high dose intake of evening primrose oil on plasma and cellular fatty acid compositions, alpha tocopherol levels and erythropoiesin in normal and type I (insulin-dependant) diabetic men, Diabetologia, 31, 576, 1988.
181. Uccella, R., Contini, A., and Sartorio, M., Action of evening primrose oil on cardiovascular risk factors in insulin-dependant diabetics, Clin. Ter., 129, 381, 1989.
182. Arisaka, M., Arisaka, O., and Yamashiro, Y., Fatty acid and prostaglandin metabolism in children with diabetes mellitus II. The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels, Prostaglandins Leukotr. Med., 43, 197, 1991.
183. Poisson, J.-P. et al., γ-Linolenic acid biosynthesis and chain elongation in fasting and diabetes mellitus, in γ-Linolenic Acid: Metabolism and Its Roles in Nutrition and Medicine, Huang, Y.-S. and Mills, D.E., Eds., AOCS Press, Champaign, IL, 1996, p. 252.
184. Horrobin, D.F., Gamma linolenic acid: an intermediate in essential fatty acid metabolism with potential as an ethical pharmaceutical and as a food, Rev. Contemp. Pharmacother., 1, 1, 1990.
185. Horrobin, D.F., The use of gamma linolenic acid in diabetic neuropathy, Agents Act. Suppl., 37, 120, 1992.
186. Zhu, X. and Eichberg, J., 1,2-diacylglycerol content and its arachidonyl-containing molecular species are reduced in sciatic nerve from streptoztozocin-induced diabetic rats, J. Neurochem., 55, 1087, 1990.
187. Jamal, C.A. and Carmicheal, H., The effect of gamma linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial, Diabetic Med., 7, 319, 1990.
188. Dines, K.C., Cameron, N.E., and Cotter, M.A., Comparison of the effects of evening primrose oil and triglycerides containing GLA on nerve conduction and blood flow in diabetic rats, J. Pharmacol. Exp. Ther., 273, 49, 1995.
189. Cameron, N.E. and Cotter, M.A., Comparison of the effects of ascorbyl gamma-linolenic acid and gamma-linolenic acid in the correction of neurovascular deficits in diabetic rats, Diabetologia, 39, 1047, 1996.