EFFECT OF ENDOTHELIN-1 INDUCED ISCHEMIA ON PEROXIDATIVE DAMAGE AND MEMBRANE-PROPERTIES IN RAT STRIATUM SYNAPTOSOMES

Synaptosomes obtained from rat striata lesioned by central injection o f endothelin-1 (ET-1) were analyzed for the levels of lipid peroxidati on products, the susceptibility to lipid peroxidation, the phospholipi d and free fatty acid composition and the activity of Na+,K+-ATPase on e hour after ET-1 treatment. The intrastriatal injection of ET-1 promo ted an increase of endogenous thiobarbituric reactive substances (TEAR S), as index of free radical mediated lipid damage, and a greater susc eptibility to iron/ascorbate-induced lipid peroxidation. The pattern o f free fatty acids showed a significant decrease of arachidonic and do cosahexaenoic acid consequent to ET-1 treatment. The analysis of lipid composition showed a significant loss of phospholipids: among phospho lipid species, sphingomyelin and phosphatidylethanolamine plasmalogen were particularly reduced by ET-1 treatment. The activity of membrane- bound Na+,K+-ATPase was also significantly reduced in synaptosomes obt ained from ET-1 lesioned striata. Taken together these results indicat e a significant modification of synaptosomal membrane of ET-1 treated rat striata, possibly due to a free radical mediated damage.