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Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia.
Am J Physiol. 1991 Feb; 260(2 Pt 2):H563-8.AJ

Abstract

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.

Authors+Show Affiliations

Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0570.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1996699

Citation

Betz, A L., et al. "Xanthine Oxidase Is Not a Major Source of Free Radicals in Focal Cerebral Ischemia." The American Journal of Physiology, vol. 260, no. 2 Pt 2, 1991, pp. H563-8.
Betz AL, Randall J, Martz D. Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia. Am J Physiol. 1991;260(2 Pt 2):H563-8.
Betz, A. L., Randall, J., & Martz, D. (1991). Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia. The American Journal of Physiology, 260(2 Pt 2), H563-8.
Betz AL, Randall J, Martz D. Xanthine Oxidase Is Not a Major Source of Free Radicals in Focal Cerebral Ischemia. Am J Physiol. 1991;260(2 Pt 2):H563-8. PubMed PMID: 1996699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia. AU - Betz,A L, AU - Randall,J, AU - Martz,D, PY - 1991/2/1/pubmed PY - 1991/2/1/medline PY - 1991/2/1/entrez SP - H563 EP - 8 JF - The American journal of physiology JO - Am J Physiol VL - 260 IS - 2 Pt 2 N2 - Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/1996699/Xanthine_oxidase_is_not_a_major_source_of_free_radicals_in_focal_cerebral_ischemia_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.1991.260.2.H563?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -