Accumulation of Arachidonic Acid Cyclo- and Lipoxygenase Products in Rat Brain During Ischemia and Reperfusion: Effects of Treatment with GM1-Lactone
Abstract
The aim of our study was to investigate the changes of various biochemical parameters (concentrations of lactate, free arachidonate, cyclo- and lipoxygenase products) in rat brain after ischemia and reperfusion and the effects of pre-treatment with the ganglioside derivative GM1-lactone on the same parameters. Ischemia was induced by reversible occlusion of common carotid arteries for 20 min, which in-cluded a final 5 min of respiration of 5% oxygen in nitrogen. Reperfusion was obtained by removing the occlusion. Pre-ischemic conditions were obtained on sham-operated animals. Animals were killed by microwave irradiation of their heads. Brain levels of lactate and of free arachidonate were markedly increased after ischemia and returned to normal values at 5 min of reperfusion. Levels of the cyclooxygenase metabolites prostaglandin F2α, 6-keto-prostaglandin F1α, and thromboxane B2 were increased after ischemia, whereas levels of the lipoxygenase metabolite leukotriene C, (LTC4) did not. change. After reperfusion, a very' marked increase of the cyclooxygenase products occurred but not of LTC4. Treatment with GM1-lactone prevented the elevation of cyclo- and lipoxygenase metabolites especially during reperfusion, with limited effects on lactate and free arachidonate levels.
Abbreviations used:
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- AA
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- arachidonic acid
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- CO
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- cyclooxygenase
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- DAG
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- diacylglycerol
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- EIA
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- enzymatic immunoassay
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- FFA
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- free fatty acids
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- HETE
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- hydroxyeicosatetraenoic acid
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- LTC4
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- leukotriene C4
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- LO
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- lipoxygenase
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- PGF2α
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- prostaglandin F2α; 6-keto-PGF1α, 6-keto-prostaglandin F1α
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- RIA
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- radioimmunoassay
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- TXB2
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- thromboxane B2. Ganglioside nomenclature is according to Svennerholm (1970)