Production of platelet thromboxane A2 and arterial prostacyclin I2 from hypercholesterolemic rats.

The plasma cholesterol, plasma malonaldehyde (MDA), platelet thromboxane A2 (TXA2) and vascular prostacyclin (PGI2) were measured in male Sprague-Dawley rats fed diets supplemented with cholesterol (1%) and cholic acid (0.5%). For comparisons, measurements were made in rats fed normal diets.

Metabolism of arachidonic acid in neutrophils from alloxan-diabetic rabbits.

The production of 5-lipoxygenase products from arachidonic acid was investigated in polymorphonuclear leukocytes (PMNL) isolated from non-diabetic and alloxan-induced diabetic rabbits: (i) production of 5-hydroxyeicosatetraenoic acid, leukotriene B4, and the two 6-trans-leukotriene B4 isomers were significantly decreased in the PMNL of diabetic rabbits when compared to non-diabetic rabbits; (ii) production of LTB4 and 5-HETE from diabetic PMNL required the addition of Ca2+ and A23187 to a greater degree than control incubations; and (iii) the availability of substrate in the PMNL of diabetics was not a limiting factor for 5-lipoxygenase product formation. Alternative pathways of arachidonic acid metabolism were also evaluated: the recovery of exogenous leukotriene B4 and 5-hydroxyeicosatetraenoic acid were identical using PMNL from control and diabetic rabbits and peptido-leukotrienes were not detected by radioimmunoassay. The data suggest that the activity of 5-lipoxygenase and the production of 5-hydroperoxyeicosatetraenoic acid in the diabetic PMNL may be limiting factors since the formation of leukotriene B4, leukotriene B4 isomers, and 5-hydroxyeicosatetraenoic acid are depressed in PMNL of diabetic rabbits.

Peroxide mediated effects of homocysteine on arterial prostacyclin synthesis.

The effects of homocysteine on the synthesis of arterial prostacyclin (PGI2) were investigated. Homocysteine at 10 mM and 1 mM concentration inhibited PGI2 synthesis from both exogenous and endogenous arachidonic acid. While concentrations of 100 microM and 1 microM stimulated PGI2 synthesis.

Triglyceride-lowering effect of dietary vitamin E in streptozocin-induced diabetic rats. Increased lipoprotein lipase activity in livers of diabetic rats fed high dietary vitamin E.

High vitamin E supplementation in the diets of streptozocin-induced diabetic rats eliminates accumulation of lipid peroxides in the plasma and the liver, returns the plasma triglycerides toward normal levels, and increases the activity of lipoprotein lipase. Vitamin E has no effect on the levels of insulin or glucose. These findings suggest that vitamin E increases the total hepatic triglyceride lipase activity by increasing the lipoprotein lipase activity possibly by protecting the membrane-bound lipase against peroxidative damage.

Effect of dietary vitamin E on the production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE).

Collagen and thrombin challenged platelets from vitamin E-deficient rabbits generated significantly more 12-HETE when compared to the platelets from vitamin E-supplemented rabbits. Similarly, conversion of arachidonic acid to 12-HETE was increased in platelets from vitamin E-deficient rabbits. These data show that vitamin E plays a role not only in deacylation of platelet phospholipids but also in the lipoxygenase mediated reactions.