Research Article| Volume 59, ISSUE 3, P195-202, September 1998

Evening primrose oil treatment corrects reduced conduction velocity but not depletion of arachidonic acid in nerve from streptozotocin-induced diabetic rats

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      The effects of evening primrose oil (EPO) treatment, a source of γ-linolenic acid, on the proportions of arachidonoyl-containing molecular species (ACMS) in sciatic nerve phosphatidylcholine and phosphatidylethanolamine were determined in conjunction with alterations in nerve conduction velocity. Normal and diabetic rats were either untreated or fed a dietary supplement containing isocalorically equivalent amounts of either EPO or corn oil for the duration of the experiment. After 8 weeks of streptozotocin-induced diabetes, nerve conduction velocity was reduced 16% and this deficit was prevented by either EPO or corn oil treatment. Neither EPO nor corn oil supplementation significantly increased the depressed proportions of ACMS. The level of the linoleoyl-containing molecular species, Math Eq, was elevated in the phospholipids from untreated diabetic rats and was further increased by EPO treatment. These results are consistent with decreased activity of the Δ6 desaturase that is required for arachidonic acid synthesis in vivo, but suggests that an accompanying deficit in the subsequent Δ5 desaturase-catalyzed reaction may be rate-limiting. These findings indicate that maintenance of normal ACMS levels is not required for prevention of diminished nerve conduction velocity and suggest that other factors influenced by an altered polyunsaturated fatty acid pattern, such as metabolites of linoleic acid or γ-linolenic acid other than arachidonic acid, the energy state of the nerve or the degree of membrane fluidity may contribute to impaired nerve conduction velocity in diabetic neuropathy.
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        • Dyck P.J
        • Thomas P.K
        • Asbury A.K
        • et al.
        Diabetic Neuropathy.
        W. B. Saunders, Philadelphia1987
        • Greene D.A
        • Sima A.A
        • Stevens M.J
        • et al.
        Complications: neuropathy, pathogenic considerations.
        Diabetis Care. 1992; 15: 1902-1925
        • Cameron N.E
        • Cotter M.A
        The relationship of vascular changes to metabolic factors in diabetes mellitus and their role in the development of peripheral nerve complications.
        Diab/Metab Rev. 1994; 10: 189-224
        • Holman R
        • Johnson S.B
        • Gerrard J.M
        • et al.
        Arachidonic acid deficiency in streptozotocin-induced diabetes.
        in: Proc Nat Acad Sci USA. 80. 1983: 2375-2379
        • Lin C.-J
        • Peterson R.G
        • Eichberg J
        The fatty acid composition of glycerolipids in nerve, brain and other tissues of the streptozotocin-diabetic rat.
        Neurochem Res. 1985; 10: 1453-1465
        • Zhu X
        • Eichberg J
        Molecular species composition of glycerophospholipids in rat sciatic nerve and its alteration in streptozotocin-induced diabetes.
        Biochim Biophys Acta. 1993; 1168: 1-12
        • Doss D.J
        • Kuruvilla R
        • Bianchi R
        • et al.
        Effects of hypoxia and severity of diabetes on Na, K-ATPase activity and arachidonoyl-containing molecular species in nerve from streptozotocin diabetic rats.
        Journal of the Peripheral Nervous System. 1997; 2: 155-164
        • Eck M.G
        • Wynn J.O
        • Carter W.J
        • et al.
        Fatty acid desaturation in experimental diabetes mellitus.
        Diabetes. 1979; 28: 479-485
        • Poisson J.P
        Comparative in vivo and in vitro study of the influence of experimental diabetes on rat linoleic acid 6- and 5-desaturation.
        Enzyme. 1985; 34: 1-14
        • Ramsammy L
        • Haynes B
        • Josepovitz C
        • et al.
        Mechanism of decreased arachidonic acid in the renal cortex of rats with diabetes mellitus.
        Lipids. 1993; 28: 433-439
        • Cameron N.E
        • Cotter M.A
        • Dines K.C
        • et al.
        The effects of evening primrose oil on peripheral nerve function and capillarization in streptozotocin-diabetic rats: modulation by the cyclo-oxygenase inhibitor flurbiprofen.
        Br J Pharmacol. 1993; 109: 972-979
        • Tomlinson D.R
        • Robinson J.P
        • Compton A.M
        • et al.
        Essential fatty acid diet supplementation-effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats.
        Diabetologia. 1989; 32: 655-659
        • Dines K.C
        • Cameron N.E
        • Cotter M.A
        Comparison of the effects of evening primrose oil and triglycerides containing gamma-linolenic acid on nerve conduction and blood flow in diabetic rats.
        J Pharmacol Exp Ther. 1995; 273: 49-55
        • Stevens E.J
        • Lockett M.J
        • Carrington A.L
        • et al.
        Essential fatty acid treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus.
        Diabetologia. 1993; 36: 397-401
        • Cotter M.A
        • Dines K.C
        • Cameron N.E
        Prevention and reversal of motor and sensory peripheral nerve conduction abnormalities in streptozotocin-diabetic rats by the prostacyclin analogue iloprost.
        Naunyn-Schmiedeberg's Arch Pharmacol. 1993; 347: 534-540
        • Ohno A
        • Kanazawa A
        • Tanaka A
        • et al.
        Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats.
        Diabetes Res Clin Pract. 1992; 18: 123-130
        • Yasuda H.M
        • Sonobe I
        • Hatanaka M
        • et al.
        A new prostaglandin E1 analogue (TFC-612) prevents a decrease in motor nerve conduction velocity in streptozotocin-diabetic rats.
        Biochem Biophys Res Commun. 1988; 150: 225-230
        • Hotta N
        • Koh N
        • Sakakibara F
        • et al.
        Effect of beraprost sodium, prostaglandin I2 analogue on diabetic neuropathy of rats.
        Diabetes. 1993; 42: 101
        • Keen H
        • Payan J
        • Allawi J
        • et al.
        Treatment of diabetic neuropathy with γ-linolenic acid.
        Diabetes Care. 1993; 16: 8-15
        • Shindo H
        • Tawata M
        • Aida K
        • et al.
        Clinical efficacy of a stable prostacyclin analog, iloprost, in diabetic neuropathy.
        Prostaglandins. 1991; 41: 85-96
        • Moore S.A
        • Peterson R.G
        • Felten D.L
        • et al.
        A quantitative comparison of motor and sensory conduction velocities in short- and long-term streptozotocin- and alloxan-diabetic rats.
        J Neurol Sci. 1980; 48: 133-152
        • Peterson D.B
        • Fisher K
        • Carter R.D
        • et al.
        Changes in dietary fatty acids favourably influence platelet composition in Type 2 (non-insulin-dependent) diabetes.
        Diabetologia. 1986; 29: 582
        • Sharma A.K
        • Richards P.A
        • Samad P.A
        • et al.
        Early structural abnormalities of peripheral nerves in experimental diabetes: effects of γ-linolenic acid supplementation.
        Int J Diabetes. 1997; 5: 85-94
        • Sima A.A.F
        • Brismar T
        Reversible diabetic nerve dysfunction, structural correlates to electrophysiological abnormalities.
        Ann Neurol. 1985; 18: 21-29
        • Karpen C.W
        • Pritchard K.A
        • Merola A.J
        • et al.
        Alterations of the prostacyclin-thromboxane ratio in streptozotocin-induced diabetic rats.
        Prostaglandins Leukotrienes Med. 1982; 8: 93-103
        • Cameron N.E
        • Cotter M.A
        • Robertson S
        • et al.
        Effects of gamma-linolenic acid on nerve and muscle dysfunction in experimental diabetes: relation to vascular effects of prostanoid metabolism.
        in: Horrobin D.F Treatment of Diabetic Neuropathy, a New Approach. Churchill Livingstone, Edinburgh1992: 63-82
        • Cotter M.A
        • Cameron N.E
        Effects of dietary supplementation with arachidonic acid rich oils on nerve conduction and blood flow in streptozotocin-diabetic rats.
        Prostaglandins Leukot Essent Fatty Acids. 1997; 56: 337-343
        • Fang C
        • Jiang Z
        • Tomlinson D.R
        Expression of constitutive cyclo-oxygenase (COX-1) in rats with streptozotocin-induced diabetes; effects of treatment with evening primrose oil or an aldose reductase inhibitor on COX-1 mRNA levels.
        Prostaglandins Leukot Essent Fatty Acids. 1997; 56: 157-163
        • Cameron N.E
        • Cotter M.A
        • Robertson S
        Essential fatty acid diet supplementation: Effects on peripheral nerve and skeletal muscle function and capillarization in streptozotocin-induced diabetic rats.
        Diabetes. 1991; 40: 532-539
        • Horrobin D.F
        The roles of essential fatty acids in the development of diabetic neuropathy and other complications of diabetes mellitus.
        Prostaglandins Leukot Essent Fatty Acids. 1988; 31: 181-197
        • Horrobin D.F
        • Durand L.G
        • Manku M.S
        Prostaglandin E1 modifies nerve conduction and interferes with local anaesthetic action.
        Prostaglandins. 1977; 14: 103-108
        • Yasuda H
        • Sonobe M
        • Yamashita M
        • et al.
        Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozotocin-induced diabetic rats, comparison with aldose reductase inhibitor ONO 2235.
        Diabetes. 1989; 38: 832-838
        • Malone J.I
        • Lowitt S
        • Korthals J.K
        • et al.
        The effects of hyperglycemia on nerve conduction and structure is age dependent.
        Diabetes. 1996; 45: 209-215
        • Ottlecz A
        • Sanduja S.K
        • Eichberg J
        Altered arachidonic acid metabolism in the retina of the streptozotocin-induced diabetic rat.
        Invest Ophthalmol Vis Sci. 1997; 38: S772
        • Tesfamariam B
        • Brown M.L
        • Cohen R.A
        15-Hydroxy-eicosatetraenoic acid and diabetic endothelial dysfunction in rabbit aorta.
        J Cardiovasc Pharmacol. 1995; 25: 748-755
        • Brown M.L
        • Jakubowski J.A
        • Leventis L.L
        • et al.
        Elevated glucose alters eicosanoid release from porcine aortic endothelial cells.
        J Clin Invest. 1988; 82: 2136-2141
        • Setty B.N.Y
        • Berger M
        • Stuart M.J
        13-hydroxyoctadecadienoic acid (13-HODE) stimulates prostacyclin production by endothelial cells.
        Biochem Biophys Res Commun. 1987; 146: 502-509
        • Ramsammy L.S
        • Boos C
        • Josepovitz C
        • et al.
        Biophysical and biochemical alterations of renal cortical membranes in diabetic rat.
        Biochim Biophys Acta. 1993; 1146: 1-8