The present study investigated the effect of the administration of
oxypurinol (40 mg/kg), an inhibitor of
xanthine oxidase, on
adenosine and
adenine nucleotide levels in the rat brain during
ischemia and reperfusion. The brains of the animals were microwaved before, at the end of a 20-min period of
cerebral ischemia, and after 5, 10, 45, and 90 min of reperfusion.
Cerebral ischemia was elicited by four-vessel occlusion with arterial
hypotension to 45-50 mm Hg.
Adenosine and
adenine nucleotide levels in the
oxypurinol-pretreated (administered intravenously 20 min before
ischemia) rats were compared with those in nontreated animals exposed to the same periods of
ischemia and reperfusion.
Oxypurinol administration resulted in significantly elevated
ATP levels at the end of
ischemia and 5 min after
ischemia, but not
at 10 min after
ischemia.
ADP levels were also elevated, in comparison with those in the control rats, at the end of the ischemic period. Conversely,
AMP levels were significantly reduced at the end of
ischemia and during the initial (5 min) period of reperfusion.
Adenosine levels were lower in
oxypurinol-treated rats, during
ischemia, and in the initial reperfusion phase.
Oxypurinol administration resulted in a significant increase in the energy charge both during
ischemia and after 5 min of reperfusion. Physiological indices, namely, time to recovery of mean arterial blood pressure and time to onset of respiration, were also shortened in the
oxypurinol-treated animals. These beneficial effects of
oxypurinol may have been a result of its
purine-sparing (salvage) effects and of its ability to inhibit
free radical formation by the
enzyme xanthine oxidase. Preservation of high-energy
phosphates during
ischemia likely contributes to the cerebroprotective potency of
oxypurinol.