The effects of allopurinol on the ultrastructure of ischaemic and reperfused large intestine of sheep

Department of Companion Animal Medicine and Surgery, University of Queensland.
Australian Veterinary Journal (Impact Factor: 1.05). 09/1996; 74(2):135-9. DOI: 10.1111/j.1751-0813.1996.tb14814.x
Source: PubMed


To test the possible inhibitory effect of allopurinol on reperfusion injury, caused by oxygen-derived free radicals, of sheep large intestine.
An ultrastructural study on caecal tissues from control and treated groups.
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).
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.
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.
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.

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    • "Various studies have explored the possible benefit of the administration of substances that can reduce the production of free oxygen radicals during I/R of tissues. Allopurinol and its major metabolite oxypurinol are structural analogues of the purine bases hypoxanthine and xanthine, and they competitively bind to XO. Doing this they inhibit the conversion of hypoxanthine to xanthine and further to uric acid, and they prevent the generation of superoxide and other superoxide-derived oxygen radicals.[24] Moreover, allopurinol is also claimed to be an effective scavenger of free oxygen radicals.[25] "
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    ABSTRACT: Allopurinol acts protectively in the ischemia reperfusion injury of the small intestine. The aim of this experimental study is to define the ideal time of administration of allopurinol, in experimental models of ischemia/reperfusion. We used 46 rabbits that were divided into four groups. Group A was the control. In Group B allopurinol was administered 10 min before ischemia and in Group C 2 min before reperfusion. In Group D, allopurinol was administered before ischemia and before reperfusion in half doses. Blood samples were collected at three different moments: (t1) prior to ischemia, (t2) prior to reperfusion, and (t3) after the end of the reperfusion, in order to determine superoxide dismutase (SOD) and neopterin values. Specimens of the intestine were obtained for histological analysis and determination of malondialdehyde (MDA). In Group A, mucosal lesions were more extensive compared to those of the other three groups. Similarly, MDA, SOD and neopterin values were significantly higher. On the contrary, Group D showed the mildest mucosal lesions, as well as the lowest MDA, SOD and neopterin values. Finally, the lesions and the above mentioned values were bigger in Group C than in Group D. The administration of allopurinol attenuates the production and damage effect of free oxygen radicals during ischemia reperfusion of the small intestine, thus protecting the intestinal mucosa. Its maximum beneficial action is achieved when administered both before ischemia and before reperfusion of the small intestine.
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