Protective actions of 21-aminosteroids and MK-801 on hypoxia-induced electrophysiological changes in rat hippocampal slices.
The effects of the 21-aminosteroids, U-74500A and U-78517F (drugs endowed with lipid peroxidation inhibitor properties) were tested on hypoxia-induced functional failure in rat hippocampal slices. For comparison, the effects of the non-competitive N-methyl-D-aspartate antagonist, dizocilpine (MK-801) were studied. Perfusion of slices with 50 microM of MK-801 or with 50-100 microM of U-78517F, but not with 100-200 microM of U-74500A, significantly (P < 0.01) increased the incidence of reappearance of the CA1 population spikes after reoxygenation in rat hippocampal slices subjected to a 45-min hypoxic period followed by a 45-min reoxygenation period. Perfusion of slices with 12.5 microM of MK-801 plus 12.5 microM of U-78517F significantly (P < 0.05) increased the incidence of reappearance of the CA1 population spikes after reoxygenation with respect to perfusion of slices with 12.5 microM of U-78517F alone or with 12.5 microM of MK-801 alone. The results show that 21-aminosteroids have protective effects against hypoxia-induced functional failure in rat hippocampal slices. In addition, the data show that, under the same experimental conditions, the NMDA receptor antagonist, MK-801, was also able to improve hypoxia-induced functional failure. On the whole, the results suggest that the hypoxia-induced functional electrical failure might depend on both release of excitatory amino acids and oxygen free-radical-mediated membrane lipid peroxidation.
Domenici
M R
MR
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Longo
R
R
de Carolis
A S
AS
Frank
C
C
Sagratella
S
S
D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000628:therapy*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002839:Chromans; D008054:Lipid Peroxides; D010879:Piperazines; D011281:Pregnatrienes; C066382:U 78517F; D016291:Dizocilpine Maleate; C053356:U 74500A