The effect of dietary vitamin E on the synthesis of platelet thromboxane A 2 (TxA 2 ) and vascular prostacyclin (PGI 2 ) in streptozotocin-induced diabetic rats was investigated. Thrombin-induced platelet TxA 2 synthesis in diabetic rats was significantly elevated, whereas no significant difference was found with collagen-induced synthesis. Arterial PGI 2 production was significantly decreased in diabetic rats. Serum lipid peroxide levels were elevated, and platelet vitamin E levels decreased in diabetic rats. When the diabetic rats were maintained on a high vitamin E diet for 2-3 mo, thrombin-induced platelet TxA 2 , vascular PGI 2 , and lipid peroxides were restored to levels found in nondiabetic rats. Platelets from diabetic rats maintained on a high vitamin E diet synthesized significantly less collagen-induced TxA 2 than platelets from nondietary vitamin E-supplemented diabetic rats or nondiabetic controls. DIABETES 37:947-951, November 1982.S everal studies have shown that platelets from human diabetic subjects are hypersensitive to aggregating agents 1 -2 and produce enhanced prostaglandin E 3 and TxA 2 . 2 -4 Hyperaggregability has also been demonstrated in platelets from streptozotocin-induced diabetic rats. 5 Decreased arterial PGI 2 release has been reported in diabetic rats 6 -7 and swine. 8 We have recently reported an altered balance of PGI 2 /TxA 2 in streptozotocin-induced diabetic rats. 9 Since vitamin E influences the modulation of PGI 2 /TxA 2 in nondiabetic rats, 10 we have examined in the present study the influence of dietary vitamin E on the disturbed PGI 2 /TxA 2 balance in streptozotocininduced diabetic rats.Diet. All diets were formulated by ICN Pharmaceutical Co. The basal vitamin E-deficient diet followed the formulation of Draper et al. 11 The vitamin E-supplemented diet consisted of the deficient diet supplemented with 200 mg of. vitamin E acetate per kg of diet. The control diet consisted of the deficient diet supplemented with 44 mg of vitamin E acetate per kg of diet, which the authors and ICN Pharmaceuticals have determined to be the vitamin E content (40-50 mg/kg) of normal rat chow.Prostag land ins were generously supplied by Dr. John E. Pike (Upjohn Chemical Company, Kalamazoo, Michigan). Tritiated thromboxane B 2 (150 Ci/mmol), prostaglandin E 2 . Radioimmunoassay (RIA) buffer (pH 7.6) consisted of TRIS (50 mM)-BA (0.1%). Tritiated prostag land ins were dissolved in ethanol, stored at -20°C, and diluted in RIA buffer before use. Unlabeled prostag land ins were diluted in RIA buffer and stored at -20°C. Bovine achilles-tendon collagen suspension was prepared according to Nakanishi et al., 12 and standardized using soluble calfskin collagen and the protein determination of Lowry et al. 13 Diabetes and dietary regimen. Male Sprague-Dawley rats (120-180 g) were administered streptozotocin (80 mg/kg) or vehicle (0.05 M citrate buffer, pH 4.5) through a tail vein. Glucosuria was detected within 5 days and persisted throughout the study. The rats were maintained on Purina Lab Chow...
Prostaglandins are synthesized from eicosa-8,11,14-trienoic acid and eicosa-5,8,11-14-tetraenoic acid by smooth muscle cell cultures from guinea pig aorta. Production is inhibited by indomethacin. The precursor fatty acids and their prostaglandin derivatives inhibit proliferation of the cell cultures. The relative availability of fatty acids for prostaglandin biosynthesis may represent a control mechanism for cell proliferation.
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