No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia.
Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia.
Mink
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Diving Medicine Department, Naval Medical Research Institute, Bethesda 20889-5055.
Dutka
A J
AJ
Kumaroo
K K
KK
Hallenbeck
J M
JM
D000818:Animals; D001794:Blood Pressure; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology; D004285:Dogs; D005073:Evoked Potentials, Somatosensory; D010088:Oxidoreductases / Q000378:metabolism*; D015424:Reperfusion; D014968:Xanthine Dehydrogenase / Q000378:metabolism*
D010088:Oxidoreductases; D014968:Xanthine Dehydrogenase