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.
Latini
S
S
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Pedata
F
F
Pepeu
G
G
D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014451:Ubiquinone / Q000031:analogs & derivatives
D000227:Adenine Nucleotides; D016227:Benzoquinones; D014451:Ubiquinone; D000249:Adenosine Monophosphate; D007288:Inosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C036619:idebenone; D000241:Adenosine