The effects of allopurinol on the ultrastructure of ischaemic and reperfused large intestine of sheep.
OBJECTIVE
To test the possible inhibitory effect of allopurinol on reperfusion injury, caused by oxygen-derived free radicals, of sheep large intestine.


METHODS
An ultrastructural study on caecal tissues from control and treated groups.


METHODS
Fifty sheep in four ischaemic and reperfused (treatment) groups and one control group. Three of the treatment groups were subdivided for half to be injected with allopurinol and the other half with its solvent, potassium hydroxide (KOH).


METHODS
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 ischaemia. Samples were collected before and 1 hour after induction of ischaemia and 1 min, 1 h and 8 h after reperfusion. Tissues were processed and examined with an electron microscope.


RESULTS
Untreated and solvent injected sheep showed minor ultrastructural changes following ischaemia. 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.


CONCLUSIONS
Pre-treatment with allopurinol prevented damage to tissues whereas untreated or allopurinol solvent-treated showed severe damage following reperfusion. It is believed that allopurinol, an analogue of hypoxanthine 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 preventing the formation of oxygen-derived free radicals.
Department of Companion Animal Medicine and Surgery, University of Queensland.
M
M
Ahmadinejad
M
M
Rex
R H
RH
Sutton
C C
CC
Pollitt
B
B
Cribb
D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006878:Hydroxides / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008854:Microscopy, Electron / Q000662:veterinary; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D017680:Potassium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary*; D012756:Sheep; D012757:Sheep Diseases / Q000473:pathology* / Q000517:prevention & control
D004791:Enzyme Inhibitors; D006878:Hydroxides; D017680:Potassium Compounds; D000493:Allopurinol; C029943:potassium hydroxide