EFFECT OF IDEBENONE ON ADENOSINE OUTFLOW AND ADENINE-NUCLEOTIDE LEVELIN HIPPOCAMPAL SLICES UNDER ISCHEMIA-LIKE CONDITIONS

The effect of idebenone on the changes in adenosine and nucleotide met abolism occurring in hippocampal slices after ischemia-like conditions (superfusion with glucose-free Krebs solution gassed with 95% N2-5% C O2) and during reperfusion with normal Krebs solution was investigated by measuring adenosine and inosine outflow, and adenosine and adenine nucleotide levels by HPLC. Five minutes of ischemia-like conditions b rought about an 8- and 4-fold increase in adenosine and inosine outflo w 10 min after reperfusion and a 75% increase in the tissue level of a denosine, a 40% decrease in ATP, and a 50% increase in AMP at the end of the ischemic period. Ten minutes after reperfusion, ATP and AMP ret urned to control values. Idebenone (25-100 muM) brought about a concen tration-dependent increase in adenosine and inosine outflow evoked by ischemia-like conditions. Idebenone (50 muM) also increased the adenos ine content in hippocampal slices after both ischemia (+ 150%) and rep erfusion (+ 320%). An 82% increase in ADP, 174% in AMP, and 56% in the total sum of nucleotides, 10 min after reperfusion were found in ideb enone treated slices. These results suggest that idebenone enhances ad enosine formation after ischemia-like conditions from sources other th an AMP, and improves phosphorylating activity during reperfusion. Ideb enone, by increasing adenosine and total nucleotide levels, may protec t brain tissue from ischemic damage.