allopurinol and Colonic-Diseases

Y-700, 1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, is a newly synthesized inhibitor of xanthine oxidase. This study found that feeding of Y-700 suppressed the development of colonic aberrant crypt foci, precursor lesions of colon cancer, and cell proliferation in 1,2-dimethylhydrazine-treated mice, accompanied by reduced serum urate. These results suggest that Y-700 is a useful agent for the prevention of colon tumorigenesis and that xanthine oxidase plays an important role in the development of colon cancer.

Topics: 1,2-Dimethylhydrazine; Animals; Cell Proliferation; Colon; Colonic Diseases; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred Strains; Pyrazoles; Xanthine Oxidase

Topics: Colonic Diseases; Humans; Stress, Physiological; Xanthine Oxidase

Intestinal ischemia/reperfusion provokes a local inflammatory response leading to a systemic inflammatory state. In this study we aimed to assess the effects of intestinal ischemia/reperfusion injury on anastomotic healing in the left colon with an intact vascular supply. A total of 94 Wistar albino rats were divided into three groups: sham-operated control (group I, n = 25), 30 minutes of intestinal ischemia/reperfusion (group II, n = 40), and 7-day allopurinol pretreatment and intestinal ischemia/reperfusion (group III, n = 29). After the reperfusion experiment, a segmental left colon resection and anastomosis were done. On postoperative days 3 and 7 anastomotic bursting pressure, anastomotic and operative complications, and intraabdominal adhesions were assessed. Mortality rates were 1/25, 16/40, and 4/29 for groups I, II, and III, respectively (p = 0.001). There was no difference among the groups for wound and anastomotic healing parameters evaluated by macroscopic criteria. On postoperative day 7 the mean bursting pressures were 220.3 +/- 18.5, 162.0 +/- 21.0, and 213.9 +/- 24.7 for groups I, II, and II, respectively (p = 0.000). Significantly dense adhesions were found in group II (p = 0.000). Allopurinol pretreatment prevented the effects of ischemia/reperfusion on anastomotic healing of the left colon. Intestinal/ischemia reperfusion causes impairment of anastomotic healing of the left colon. In addition to remote organ effects, reperfusion injury may affect anastomotic healing in the viscera with an intact vascular supply.

Topics: Allopurinol; Anastomosis, Surgical; Animals; Colon; Colonic Diseases; Female; Free Radical Scavengers; Postoperative Complications; Rats; Rats, Wistar; Reperfusion Injury; Tissue Adhesions; Wound Healing

The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (week 5), AOM induced 118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with suppression of the proliferation biomarkers' expression such as ornithine decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine content. These results indicate that ACA could inhibit the development of AOM-induced ACF through its suppression of cell proliferation in the colonic mucosa and ACA might be a possible chemopreventive agent against colon tumourigenesis.

Topics: Animals; Antineoplastic Agents; Azoxymethane; Benzyl Alcohols; Body Weight; Cell Division; Colon; Colonic Diseases; Enzyme Inhibitors; Intestinal Mucosa; Liver; Male; Organ Size; Ornithine Decarboxylase; Polyamines; Precancerous Conditions; Rats; Rats, Inbred F344; Terpenes; Xanthine Oxidase