Effect of idebenone on adenosine outflow and adenine nucleotide level in hippocampal slices under ischemia-like conditions.

The effect of idebenone on the changes in adenosine and nucleotide metabolism occurring in hippocampal slices after ischemia-like conditions (superfusion with glucose-free Krebs solution gassed with 95% N2-5% CO2) 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 brought about an 8- and 4-fold increase in adenosine and inosine outflow 10 min after reperfusion and a 75% increase in the tissue level of adenosine, 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 returned to control values. Idebenone (25-100 microM) brought about a concentration-dependent increase in adenosine and inosine outflow evoked by ischemia-like conditions. Idebenone (50 microM) also increased the adenosine content in hippocampal slices after both ischemia (+150%) and reperfusion (+320%). An 82% increase in ADP, 174% in AMP, and 56% in the total sum of nucleotides, 10 min after reperfusion were found in idebenone treated slices. These results suggest that idebenone enhances adenosine formation after ischemia-like conditions from sources other than AMP, and improves phosphorylating activity during reperfusion. Idebenone, by increasing adenosine and total nucleotide levels, may protect brain tissue from ischemic damage.