[The effect of phenytoin on free fatty acid liberation and mononucleotide metabolism in transient ischemia].
Ischemia gives rise to severe energy depletion and influx of Ca from the extracellular space, and it is suggested that increased intracellular Ca leads to the activation of phospholipase C and A, and to liberation of free fatty acids (FFA) in particular arachidonic acid. Phenytoin has been reported not only to maintain the intra- and extracellular cation balance but blockade the Ca channel. The purpose of the present study is to investigate the effect of phenytoin on the liberation of FFA, energy metabolism and mononucleotide metabolism in ischemic brain. Male Wistar rats were subjected to global cerebral ischemia induced by the occlusion of basilar and bilateral common carotid arteries. The brains were frozen in situ by the funnel technique after 5 or 30 min of ischemia or after 10, 30, or 60 min of recirculation following 30 min of ischemia. Purine and pyrimidine nucleotides, FFA, and glycolytic intermediates were measured by HPLC, GLC, and fluoro-enzymatic method. In non-treated rats, ATP reached a nadir after 5 and 30 min of ischemia. Phenytoin significantly attenuated ATP depletion after 5 and 30 min of ischemia. And also E.C. is higher in phenytoin treated rats than in non-treated rats in ischemia. After 60 min of recirculation, ATP recovered to 1.93 +/- 0.02 mumol (72.3% of pre-ischemia) in treated rats but 1.60 +/- 0.07 mumol/g (60% of pre-ischemia) in non treated rats. In E.C., there are significant differences between non-treated and treated rats after 10 and 30 min of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinouchi
H
H
Division of Neurosurgery, School of Medicine, Tohoku University, Sendai, Japan.
Imaizumi
S
S
Suzuki
J
J
Yoshimoto
T
T
Motomiya
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D005110:Extracellular Space / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D010672:Phenytoin / Q000494:pharmacology*; D011685:Purine Nucleotides / Q000378:metabolism*; D011742:Pyrimidine Nucleotides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005230:Fatty Acids, Nonesterified; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D010672:Phenytoin; D002118:Calcium