Effect of stobadine on the inhibition of translation induced by ischemia and subsequent reperfusion in the rat brain

The ability of stobadine to prevent inhibition of proteosynthesis was exami ned in incomplete forebrain ischemia that was induced by a 4-vessel occlusi on model and subsequent reperfusion. The extent of inhibition was determine d by the measurement of labelled leucine incorporation into polypeptide cha ins in the cell free system and the activity of eukaryotic initiation facto r 2 (eIF-2). Both labelled leucine incorporation into proteins and the acti vity of eIF-2 were significantly inhibited in brain cortex samples from ani mals subjected to ischemia followed by reoxygenation in comparison with isc hemic samples without reperfusion, or control samples from sham operated an imals. Whereas the effect of therapeutic doses of stobadine, (5 mg/kg) admi nistered i.p. 15 min before ischemia, on leucine incorporation was low in s amples from ischemia without reperfusion, stobadine significantly prevented inhibition occuring in the first minutes of reperfusion. Favourable impact of stobadine was higher in the assay of ternary complex formation (activit y of eIF-2) than in the leucine incorporation into polypeptides. It may be concluded that: 1) free oxygen radicals probably play a significant role in postischemic inhibition of translation; 2) stobadine very effectively prev ents deprivation of the reinitiation ability of the proteosynthetic machine ry and the activity of eIF-2.