THE EFFECTS OF ALLOPURINOL ON THE ULTRASTRUCTURE OF ISCHEMIC AND REPERFUSED LARGE-INTESTINE OF SHEEP

Objective: To test the possible inhibitory effect of allopurinol on re perfusion injury, caused by oxygen-derived free radicals, of sheep lar ge intestine. Design: An ultrastructural study on caecal tissues from control and treated groups. Animals: Fifty sheep in four ischaemic and reperfused (treatment) groups and one control group. Three of the tre atment groups were subdivided for half to be injected with allopurinol and the other half with its solvent, potassium hydroxide (KOH). Proce dure: Ischaemia of the caecum was induced in the four treatment groups for 60 minutes by clamping the apex. Allopurinol and its KOH solvent were injected intravenously in three treatment groups prior to ischaem ia. Samples were collected before and 1 hour after induction of ischae mia and 1 min, 1 h and 8 h after reperfusion. Tissues were processed a nd examined with an electron microscope. Results: Untreated and solven t injected sheep showed minor ultrastructural changes following ischae mia. With reperfusion, there was severe mitochondrial, goblet cell and basement membrane damage. Tissues from allopurinol-treated sheep were preserved and appeared similar to tissues from the control group. Con clusion: Pre-treatment with allopurinol prevented damage to tissues wh ereas untreated or allopurinol solvent-treated showed severe damage fo llowing reperfusion. It is believed that allopurinol, an analogue of h ypoxanthine and xanthine, prevents reperfusion injury by competitively binding with xanthine oxidase. This reduces or inhibits the xanthine oxidase mediated conversion of hypoxanthine to xanthine thereby preven ting the formation of oxygen-derived free radicals.