The effect of quinolinate on rat brain lipid peroxidation is dependent on iron.
Quinolinate, an endogenous excitotoxic metabolite of tryptophan with affinity to the N-methyl-D-aspartate type of glutamate receptor, is known as a stimulator of lipid peroxidation in vitro [Neurochem. Res. (1991) 16, 1139-1143]. To analyse the mechanism of this quinolinate toxicity we used the thiobarbituric acid test to measure malondialdehyde in homogenates of rat cerebral hemispheres incubated in air at 37 degrees C for 30 min in the presence of 0.015-15.0 mM quinolinate, endogenous iron or 0.5-2.0 microM FeSO4 and with or without 250 microM ascorbate. Quinolinate in the concentrations of 0.15-2.5 mM stimulated lipid peroxidation in the homogenates in the presence of 0.5-2.0 microM Fe2+. However, quinolinate concentrations higher than 3.0 mM inhibited the lipid peroxidation at all the tested concentrations of iron. In the presence of a potent iron chelator (10 microM deferoxamine) quinolinate completely failed to induce lipid peroxidation in rat brain homogenates. Spectral analysis revealed that quinolinate is able to form a complex with Fe2+. The results suggest that quinolinate does not have a direct peroxidative effect, but that it modulates lipid peroxidation via its interaction with iron.
Stípek
S
S
First Department of Medical Chemistry and Biochemistry, First Medical Faculty, Charles University, Prague, Czech Republic.
Stastný
F
F
Pláteník
J
J
Crkovská
J
J
Zima
T
T
D000818:Animals; D001205:Ascorbic Acid / Q000037:antagonists & inhibitors*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017262:Siderophores / Q000494:pharmacology
D007502:Iron Chelating Agents; D017262:Siderophores; D017378:Quinolinic Acid; D003676:Deferoxamine; D001205:Ascorbic Acid