Allopurinol's effect on caspase-3 and caspase-8 in hypoxic-ischemic newborn rats

Aim: During reperfusion period of hypoxia-ischemia, cyclooxygenase and xanthine oxidase pathways are induced. Free oxygen radicals activate adhesion molecules on leukocytes, platelets and endothelial cells and activate leucocytes? adhesion and extravasation. A xanthine oxidase inhibitor, allopurinol has been shown to be neuroprotective in hypoxic- ischemic encephalopathy. Caspase-8 and caspase-3 have a key role in neuronal apoptosis. We aimed to investigate different dosages of allopurinol?s effect on caspase-3 and caspase-8 activities in newborn rats with hypoxic-ischemic encephalopathy.Material and method: 10 days old newborn rats were enrolled to the study. Rice?s hypoxia-ischemia model were used. Left carotid artery was ligated and rats were perfused with 8% oxygen and 92% nitrogen for two and half hours (HI group). Rats were treated with allopurinol and caspase- 3 and caspase- 8 activities were measured in both hemispheres. AL48 group was treated with 24 mg/kg intraperitoneal allopurinol 30 minutes and 12 hours after hypoxic- ischemic insult; while AL72 group was treated with same dose after 30 minutes, 12 hours and 24 hours. Twelve hours after last dose, rats were decapitated. The others groups were sham and non- treated hypoxic- ischemic (HI) group.Results: There were 10 rats in each group. There was no significance between gender and weights among groups (p>0.05). Caspase-3 and 8 activities were significantly higher in HI, AL48 and AL72 groups compared to sham group (p=0,0001, for all, respectively). Although caspase activities were not different in HI and AL48 groups (p>0.05), the activities were lower in AL72 group compared to HI and AL48 groups (p=0,0001, for each).Conclusion: Decreased activities of caspase- 3 and 8 in AL72 groups may suggest that high dose of allopurinol may be effective for reducing neuronal apoptosis.