A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats

The modifying effect of dietary administration of a xanthine oxidaseinhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plantLanguas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. MaleF344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a weekfor 3 weeks to induce colonic ACF. They were fed the diets containing 100or 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 frequencyof ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppmACA feeding, P<0.01). Such inhibition might be associated withsuppression of the proliferation biomarkers' expression such as ornithinedecarboxylase activity in the colonic mucosa, number of silver-stainednucleolar organizer regions' protein in the colonic mucosal cell nuclei andblood polyamine content. These results indicate that ACA could inhibit thedevelopment of AOM-induced ACF through its suppression of cellproliferation in the colonic mucosa and ACA might be a possiblechemopreventive agent against colon tumourigenesis.