The effects of allopurinol on the ultrastructure of ischaemic and reperfused large intestine of sheep.
ABSTRACT 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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ABSTRACT: The purpose of the study was to evaluate ischaemia/reperfusion injury in simulated abomasal volvulus in sheep. Sixteen ewes were randomly allocated to three groups. The control group (n=4) served as sham-operated controls. The animals of the ischaemia group and reperfusion group (n=6, each) underwent a simulated 'abomasal volvulus'. The abomasum was exteriorized under general inhalation anesthesia and forced into a 180( composite function) anticlockwise rotation around its longitudinal axis, followed by another 270( composite function) anticlockwise rotation around its transectional axis. All ewes were monitored for 4 h. In the reperfusion group, volvulus was released after 3 h (i.e., 1 h of reperfusion). In the ischaemia group, the volvulus remained for 4 h (no reperfusion). Vital signs were monitored and some haematological and biochemical parameters were measured, without any significant differences. Full-section biopsy specimens were taken at the 3rd and 4th hours from the greater curvature of the abomasum. Histopathological lesions were scored according to the severity of mucosal oedema, submucosal oedema, haemorrhage submucosal and submuscularis layers, and polymorphonuclear infiltration on a scale of 0 to 4 (nil, mild, moderate, severe, and extreme). Another biopsy specimen was taken at the 4th hour for transmission electron microscopic examination. The scored lesions in light-microscopic examination were significantly different at the 3rd and 4th hours between the control and the experimental groups (p<0.05). There was no significant difference between the reperfusion and ischaemia groups (p>0.1). Within-group comparisons (3rd hour with 4th hour) revealed no significant differences. In transmission electron microscopic examination there were no remarkable changes in the control group, but in the ischaemia and reperfusion groups there were remarkable cellular (epithelial and goblet cells), mitochondrial and microvillous changes that strongly implied the occurrence of ischaemia (p<0.05). In transmission electron-microscopic examination of abomasal samples the lesions were more remarkable in reperfusion group than in the ischaemia group. It is concluded that ischaemia/reperfusion injury occurred in this model of simulated abomasal volvulus in sheep and that ischaemia/reperfusion injury should be considered as a potential determining factor in the outcome of cattle with abomasal volvulus.Veterinary Research Communications 08/2007; 31(5):575-90. · 1.08 Impact Factor
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ABSTRACT: BACKGROUND: Xanthine oxidase has been implicated in the pathogenesis of a wide spectrum of diseases, and is thought to be the most important source of oxygen-free radicals and cell damage during re-oxygenation of hypoxic tissues. AIMS: The present study was undertaken to demonstrate whether febuxostat is superior to allopurinol in prevention of the local and remote harmful effects of small intestinal ischemia/reperfusion injury in rats. METHODS: Intestinal ischemia was induced by superior mesenteric artery ligation. The rats were assigned to five groups: the sham control; the intestinal ischemia/reperfusion; the allopurinol; and the febuxostat 5 and 10 mg/kg pretreated ischemia/reperfusion groups. Treatment was administered from 7 days before ischemia induction. After the reperfusion, the serum and tissues were obtained for biochemical, pharmacological, and histological studies. RESULTS: Intestinal reperfusion led to an elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, malondialdehyde, and xanthine oxidase as well as intestinal myeloperoxidase, malonadialdehyde, and xanthine oxidase/xanthine dehydrogenase activity. Furthermore, the ischemia/reperfusion induced a reduction in the contractile responsiveness to acetylcholine. These changes were significantly regulated by the pretreatment with febuxostat compared to allopurinol. The degree of pathological impairment in the intestinal mucosa, liver, and lung tissues were lighter in the pretreated groups. CONCLUSIONS: Febuxostat may offer advantages over allopurinol in lessening local intestinal injury as well as remote hepatic and lung injuries induced by small intestinal ischemia/reperfusion.Digestive Diseases and Sciences 09/2012; · 2.26 Impact Factor
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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.Journal of Emergencies Trauma and Shock 07/2013; 6(3):203-8.