Unbalanced plasma control of TxA2 and PGI2 synthesis in vitamin E-deficient rats

Abstract

Factors contributing to the antioxidant power of plasma may play a role in the control of arachidonic acid (AA) metabolism. The purpose of this study was to evaluate the possible effects of vitamin E deficiency on platelet and vascular prostaglandin synthesis. CD-COBS male rats were fed for 7 mo a diet containing either 1 or 75 mg/kg vitamin E. At the end of this period, serum levels of vitamin E were 0.4 +/- 0.1 and 10 +/- 0.6 micrograms/ml in the two groups, respectively. Malondialdehyde (MDA) generation by AA was significantly higher in platelet-rich plasma from vitamin E-deficient rats. Thromboxane B2 (TxB2) in serum from vitamin E-deficient rats increased about 16 times compared with controls, whereas 6-keto-PGF1 alpha levels increased only 3 times. The ratio between TxB2 and 6-keto-PGF1 alpha, increased therefore manyfold in vitamin E-deficient animals. MDA formation and [14C]AA metabolism in washed platelets were similar in the two groups of animals. No significant difference was found in the PGI2 (prostacyclin) antiaggregating activity released from the aortic rings resuspended in buffer. In contrast, the capacity of plasma to stimulate PGI2 activity from "exhausted" aortic rings (prostacyclin-stimulating factor) was significantly reduced in vitamin E-deficient animals. In conclusion, vitamin E deficiency induces an unbalanced plasma regulation of AA metabolism. This results in an excessive production of platelet TxA2 compared with vascular PGI2 generation. On the other hand, vitamin E deficiency does not seem to affect directly the enzymatic pathways of AA metabolism.

Vitamin E Intake Affects Serum Thromboxane and Tissue Essential Fatty Acid Composition in the Rat

“…However, based on plasma and tissue PL levels of 20:4n-6, 22:6n-3 and 22:5n-6 (testes) in the vitamin E(-) group, lipid peroxidation which may have existed did not affect the net composi tion of long chain fatty acids in plasma or tissue PL. In agreement with previous re ports [14][15][16], thromboxane Bj synthesis (which involves synthesis of a hydroperoxy derivative of 20:4n-6 via thromboxane syn thetase) in clotting blood was 49% greater in the vitamin E(-) group than in controls (ta ble I) suggesting weaker control of enzymatic peroxidation of 20:4n-6 in platelets of the vitamin E(-) rats. In spite of the increase in platelet thromboxane generation, platelet fatty acid composition has been shown to remain unaffected by vitamin E deficiency in the rat [17,18].…”

Review articles

“…The protective effects of vitamin E are probably far more complex than only a beneficial effect of the PGI 2 /TXA 2 balance [30]. Animal studies demonstrate that vitamin E may be beneficial in J. Perinat Med.…”

Copper-Marginal and Copper-Deficient Diets Decrease Aortic Prostacyclin Production and Copper-Dependent Superoxide Dismutase Activity, and Increase Aortic Lipid Peroxidation in Rats

“…Vitamin E was added to all diets at a final concentration of 50.0 mg all-rac-atocopherol/kg diet by mixing the vitamin with the vitamin E-stripped corn oil before adding it to the diet. Vitamin E-stripped corn oil with controlled ad dition of both vitamin E and selenium was used be cause deficiencies of either have been shown to in fluence aortic prostacyclin synthesis (Falanga et al 1983, Schoene et al 1986. At entry all rats in the three groups were allowed ad libitum access to the CuD diet containing 0.1% (by weight) specific copper chelator N,AT-bis (2-aminoethyl)-l,3-propanediamine-4HC1 (2,3, for 1 wk to deplete body copper stores.…”