All issues > Volume 45(6); 2002

Original Article

J Korean Pediatr Soc. 2002;45(6):732-742. Published online June 15, 2002.

Effect of Xanthine Oxidase Inhibitor on Cerebral Hypoxia-Ischemia in Neonatal Rats

Dae-Ho DH Choi¹, Yeon-Kyun YK Oh¹, Seung-Tak ST Park²

¹Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
²Department of Anatomy, Wonkwang University School of Medicine, Iksan, Korea

Correspondence Yeon-Kyun YK Oh ,Email: oyk5412@wonkwang.ac.kr

Abstract

Purpose
: In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes.
Methods
: Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day old neonatal rats which were subjected to unilateral common carotid artery occlusion and exposed to hypoxic condition for 3 hours. The protective effect of XO inhibitor was examined by the cell number, cell viability, LDH and PS on 14 days after H-I with allopurinol intraperitoneal injection 15 minutes prior to H-I. In addition, the effect of allopurinol on PKC activity in hypoxic conditions was examined in neurons.
Results
: 72 hours from H-I, the cell numbers and viability were decreased significantly in time- dependent manner on neurons and those of astrocytes also decreased slightly, compared with control. In neonatal rats treated with H-I, the cell number, cell viability, and PS in neurons were decreased, but LDH was increased significantly compared with control. In neonatal rats pretreated with allopurinol, the cell number and viability, and PS in neurons were increased and LDH was decreased significantly compared with H-I. PKC was increased remarkably after hypoxic condition. But PKC was decreased significantly against hypoxic condition after allopurinol pretreatment.
Conclusion
: From these results, it is suggested that H-I is more toxic in neurons than astrocytes and allopurinol is very protective with increasing of PS, and decreasing of LDH and PKC in neurons from hypoxic-ischemic condition.

Keywords :Hypoxia-ischemia, Xanthine oxidase inhibitor, Allopurinol, L오, Protein synthesis, PKC