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 pretreatment with the ganglioside derivative GM1-lactone on the same parameters. Ischemia was induced by reversible occlusion of common carotid arteries for 20 min, which included 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 F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were increased after ischemia, whereas levels of the lipoxygenase metabolite leukotriene C4 (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.

Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats.

“…Our findings are consistent with previous reports demonstrating that systemic treatment with monosialoganglioside (GM1 or its inner ester derivative, siagoside) is efficacious in limiting mortality and the loss of hemispheric Na,K-ATPase activity in gerbils subjected to permanent unilateral carotid artery occlusion 11 ; brain edema, Na + and Ca 2+ intracellular loading, and behavioral deficits following focal cortical ischemia in rats 11 ; elevated concentrations of cyclooxygenase and lipoxygenase metabolites after transient hypoxia-ischemia in rats 12 ; morphologic damage and neurologic deficits subsequent to transient middle cerebral artery occlusion in cats 21 ; and neurologic impairment after global cerebral ischemia in monkeys. 10 The molecular mechanisms underlying the capability of siagoside to limit neuronal damage after a cerebral hypoxic/ischemic insult remain to be fully denned.…”

“…We designed the present investigation to evaluate the capability of the inner ester derivative of GM1 (designated siagoside in our study and GMl-lactone 12 or AGF2 9 by others) to limit neuronal damage over time following transitory near-complete forebrain ischemia in adult rats.…”

Formation of eicosanoids, E2/D2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain

“…The unesterified AA is rapidly esterified to available lysophospholipids (5,6), or is converted into eicosanoids via cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 epoxygenase enzymes. Increased brain levels of prostaglandin E 2 (PGE 2 ), PGD 2 , and thromboxane B 2 (TXB 2 ), formed via COX pathways, and of hydroxyeicosatetraenoic acid (HETE), LTB 4 , and LTC 4 , formed via LOX pathways, have been reported following cerebral ischemia (7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Effect of Cyclooxygenase Inhibition on Brain Cell Membrane Lipid Peroxidation during Hypoxia in Newborn Piglets

“…Arachidonic acid is released from cell membranes during cerebral hypoxia [14,15]. Metabolism of free arachidonic acid results in production of oxygen free radicals via both the cyclooxygenase and lipoxygenase path ways [16], Indomethacin, an inhibitor of cy clooxygenase, reduces the production of free radicals by preventing the conversion of ara chidonic acid to prostanoids [16], and has been shown to alter the cerebral circulatory and metabolic response to hypoxia [17,18].…”