Synaptosomal iron-dependent lipid peroxidation inhibition after subarachnoid hemorrhage by lazaroid in vivo treatment.
The production of oxygen-free radicals and their subsequent peroxidative action on membrane unsaturated fatty acids could be enhanced after subarachnoid hemorrhage (SAH). We have studied the effects of the in vivo pharmacological treatment with a lazaroid (U78517F) after experimental SAH, on lipid peroxidative patterns in cortical synaptosomal preparations. U78517F is a lipid-soluble antioxidant with a potent action to inhibit iron-dependent lipid peroxidation. Experimental SAH was induced in anesthetized rats by slow injection of 0.3 mL of autologous arterial blood into cisterna magna. The hemorrhagic animals were treated with 5 mg/kg iv of U78517F immediately after surgical operation. The animals were sacrificed 1 d after the hemorrhage and the thiobarbituric acid reactive material (TBAR) was assayed in basal conditions and after 1, 3, 5, 10, and 20 min of incubation at 37 degrees C with a pro-oxidant mixture on three different rat groups: sham-operated (0.3 mL of mock cerebrospinal fluid (CSF) into cisterna magna), hemorrhagic (0.3 mL of autologous arterial blood into cisterna magna), and hemorrhagic-treated. The hemorrhagic event did not influence the membrane lipoperoxidation levels in basal conditions, whereas peroxidative stimulation in vitro caused significant increases in hemorrhagic animals compared to the sham-operated, and in hemorrhagic-treated animals, the synaptosomal TBARs were similar to controls. The pharmacological treatment showed its effectiveness only following incubations with pro-oxidants; therefore, U78517F seems to be protective for membranes in case of severe lipid peroxidative stress.
Torri
C
C
Institute of Pharmacology, University of Pavia, Italy.
Café
C
C
Adinolfi
D
D
Gaetani
P
P
Rodriguez y Baena
R
R
Marzatico
F
F
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001804:Blood Transfusion, Autologous; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000097:blood; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors
D000975:Antioxidants; D002839:Chromans; D010879:Piperazines; D017392:Thiobarbituric Acid Reactive Substances; C066382:U 78517F; D002245:Carbon Dioxide; D007501:Iron; D010100:Oxygen