Arachidonic Acid Metabolism In Human Platelets Research Articles

The effect of aqueous garlic extract on the levels of arachidonic acid metabolites (leukotriene C 4 and prostaglandin E 2) in rat forebrain after ischemia-reperfusion injury

Leukotriene C 4 (LTC 4) and prostaglandin E 2 (PGE 2) are known to be highly potent cerebral vasoconstrictors which are formed from arachidonic acid (AA). They enhance vascular permeability, inducing vasogenic edema that may damage the ischemic penumbra after ischemia and reperfusion. The inhibitory effect of aqueous garlic extract (AGE) on AA metabolism in human platelets is known. In this study, following the global ischemic model application to the rats, all underwent 10 min ischemia and were reperfused for different periods. The levels of LTC 4 and PGE 2 in rat forebrain were then measured. One rat group consisted of 8 rats. In the combined reperfused groups both metabolites increased significantly when compared with the 10 min ischemia alone, no reperfusion group ( P < 0.05). In the 8 min reperfused group, PGE 2 and LTC 4 levels increased significantly at 60 min of reperfusion compared with each corresponding control group ( P < 0.005). PGE 2 and LTC 4 levels were reduced significantly at 60 min of reperfusion compared with the 8 min reperfused group ( P < 0.005). AGE (1 ml/kg) reduced both LTC 4 and PGE 2 levels significantly in the 8 min and 60 min reperfused group ( P < 0.001, P < 0.001, P < 0.05, P < 0.01). In conclusion, AGE reduced LTC 4 and PGE 2 levels at a dosage of 1 ml/kg following 8 and 60 min reperfusion. It may be helpful in reducing AA metabolite levels and preventing injury after ischemic phenomena.

Role of glutathione and glutathione peroxidase in human platelet arachidonic acid metabolism

Selective removal of intracellular glutathione (GSH) and inhibition of the GSH-dependent peroxidase (GSH-Px) by 1-chloro-2, 4-dinitrobenzene (CDNB) was used to evaluate the role of GSH and GSH-Px in arachidonic acid (AA) metabolism in human platelets. Although total conversion of AA through the lipoxygenase pathway is lowered by GSH depletion, significant 12-HETE formation was observed suggesting that GSH and GSH-Px are not required for the generation of 12-HETE in human platelets. Prolonged treatment of platelets with CDNB (2 h) completely destroyed GSH-Px activity creating a model in which the effects of GSH alone could be determined. Platelet homogenates replenished with GSH, but lacking GSH-Px activity converted significantly higher amounts of AA to 12-HPETE and 12-HETE than control. Platelet cytosolic metabolism of 15-HPETE to 15-HETE decreased after CDNB, while the membrane metabolism remained similar to control due to high GSH-independent peroxidase activity associated with the membranes. These results indicate that GSH and GSH-Px function to enhance lipoxygenase activity, rather than catalyse the reduction of 12-HPETE to 12-HETE.

The influence of albumin and calcium on human platelet arachidonic acid metabolism

The effects of in vitro changes in calcium and albumin on human platelet arachidonic acid metabolism were evaluated. Hypoalbuminemia enhanced the conversion of released 14C-arachidonic acid from prelabeled platelet phospholipids to the metabolites of the platelet cyclooxygenase and lipoxygenase pathways. This effect was, however, associated with a decreased release of arachidonic acid in the presence of hypoalbuminemia, such that the overall conversion of released 14C- arachidonic acid to platelet thromboxane B2 was similar in the presence of physiologic albumin concentration (3.5 g/dl) or at decreased albumin concentrations of 0.7 and 0.0 g/dl. External calcium was shown to be important for optimal platelet arachidonic acid release, with maximal release occurring at 1 mM calcium.

The Influence of Albumin and Calcium on Human Platelet Arachidonic Acid Metabolism

The effects of in vitro changes in calcium and albumin on human platelet arachidonic acid metabolism were evaluated. Hypoalbuminemia enhanced the conversion of released 14C-arachidonic acid from prelabeled platelet phospholipids to the metabolites of the platelet cyclooxygenase and lipoxygenase pathways. This effect was, however, associated with a decreased release of arachidonic acid in the presence of hypoalbuminemia, such that the overall conversion of released 14C-arachidonic acid to platelet thromboxane B2 was similar in the presence of physiologic albumin concentration (3.5 g/dl) or at decreased albumin concentrations of 0.7 and 0.0 g/dl. External calcium was shown to be important for optimal platelet arachidonic acid release, with maximal release occurring at 1 mM calcium.