SYNAPTOSOMAL IRON-DEPENDENT LIPID-PEROXIDATION INHIBITION AFTER SUBARACHNOID HEMORRHAGE BY LAZAROID IN-VIVO TREATMENT

The production of oxygen-free radicals and their subsequent peroxidati ve action on membrane unsaturated fatty acids could be enhanced after subarachnoid hemorrhage (SAH). We have studied the effects of the in v ivo pharmacological treatment with a lazaroid (U78517F) after experime ntal SAH, on lipid peroxidative patterns in cortical synaptosomal prep arations. U78517F is a lipid-soluble antioxidant with a potent action to inhibit iron-dependent lipid peroxidation. Experimental SAH was ind uced in anesthetized rats by slow injection of 0.3 mt of autologous ar terial blood into cisterna magna. The hemorrhagic animals were treated with 5 mg/kg iv of U78517F immediately after surgical operation. The animals were sacrificed Id after the hemorrhage and the thiobarbituric acid reactive material (TBAR) was assayed in basal conditions and aft er. 1, 3, 5, 10, and 20 min of incubation at 37 degrees C with a pro-o xidant mixture on three different rat groups: sham-operated (0.3 mt 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 lipoper oxidation 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 synapto somal TBARs were similar to controls. The pharmacological treatment sh owed its effectiveness only following incubations with pro-oxidants; t herefore, U78517F seems to be protective for membranes in case of seve re lipid peroxidative stress.