The effects of the xanthine oxidase inhibitors, allopurinol and oxypurinol on the pattern of purine release from hypoxic rat cerebral cortex.
Release of purines from the normoxic and hypoxic/ischemic rat cerebral cortex was studied with the cortical cup technique. Both allopurinol (100 mg/kg, i.v.) and its active metabolite oxypurinol (20 mg/kg, i.v.) reduced the release of uric acid to 10% of predrug levels, indicating an effective block of xanthine oxidase activity. Xanthine and hypoxanthine, substrates for xanthine oxidase, increased in the cortical perfusates following drug administration. Allopurinol treatment resulted in a decreased release of adenosine during the first postdrug hypoxic challenge, whereas oxypurinol, and allopurinol during the second postdrug challenge, increased the hypoxia-evoked level of adenosine and inosine in the perfusate. The purine sparing effects of allopurinol and oxypurinol, in addition to the prevention of xanthine oxidase-mediated free radical generation, may account for their protective action in reperfusion injury paradigms.
O'Regan
M H
MH
Department of Physiology, Wayne State University, School of Medicine, 540 E. Canfield, Detroit, MI 48201, U.S.A.
Phillis
J W
JW
Walter
G A
GA