ALMITRINE PREVENTS SOME HYPOXIA-INDUCED METABOLIC INJURY IN RAT ASTROCYTES

During reperfusion of ischemic brain tissue, the production of reactiv e oxygen species initiates several modifications of the astroglial fun ctional and ultrastructural integrity. During 24 h after ischemic trea tment, modification of cellular superoxide free radical scavenging sys tems have been observed in primary culture of rat astroglial cell. Mit ochondrial Mn superoxide dismutase activity (Mn-SOD) gradually decreas es, whereas that of the cytosolic Cu,Zn form of the enzyme remains una ffected. We observed in parallel a significant decrease of glutamine s ynthetase (GS), an astrocyte specifically located enzyme. Addition of almitrine (dialylamine-4',6'-triazinyl 2')-1-(bis-parafluorobenzydryl) -4-piperazine or dibucaine (a phospholipase A2 inhibitor) antagonizes the decrease of Mn-SOD activity, but does not affect modification of G S activity. Combined effects are observed by simultaneous addition of both drugs. Our data demonstrate that almitrine may increase the synth esis of some mitochondrial proteins, like Mn-SOD, and provide support for further study on the therapeutic potential of almitrine in ischemi c astroglial cell injury.