A comparison of nondigestible carbohydrate and a natural and synthetic anti-inflammatory agent on azoxymethane (AOM) -induced aberrant crypt foci (ACF) in Fisher 344 male rats.

A63

Colon cancer is a leading cause of morbidity and mortality. Non-digestible carbohydrates and non-steroidal anti-inflammatory drugs (NSAID's) have shown potential as chemopreventive agents. The objective of this study was to test the effect of feeding BENEO®Synergy1 (long chain inulin + oligofructose ) singly and in combination, with Aspirin and curcumin on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 rats. Following a one week period of acclimatization 60 male weanling rats were divided into 6 groups and fed AIN93G (Control-C) and 7 experimental groups; C+ Synergy1, C + Aspirin, C + curcumin, C + Synergy1 + Aspirin and C + Synergy1 + Curcumin. All rats received s/c injections of AOM at 16mg/kg body weight in saline. Weekly body weights and daily feed intakes were recorded. At 17 wk of age all the rats were killed by CO₂ asphyxiation. Cecal pH and cecal weight were recorded. Hepatic Glutathione-S-Transferase (GST), a crucial phase II detoxification enzyme was analyzed. There were no differences in weight gain or feed intake among control and experimental groups. However there was a significant (p<0.05) increase in cecal weight and decrease in cecal pH in groups fed Synergy 1 compared to the control group. Number of ACF were significantly lower (p<0.05) in groups fed Synergy 1, Aspirin and Curcumin. The percent reduction in total ACF in dietary treatments when compared to control were 52.8 (C+ Synergy1), 50.1 (C + Aspirin ), 70.3 (C + Synergy1 + Aspirin) and 78.4 (C + Synergy1 + curcumin). The size of the ACF expressed as the number of aberrant crypts/ ACF or crypt multiplicity were significantly higher in the rats fed control compared with rats fed Synergy1, Aspirin and Curcumin singly and in combination, with the rats fed C + Synergy1 + curcumin having the lowest number of aberrant crypts/ACF. Glutathione-S- transferase activity was significantly higher in the treatment groups compared to the control. This study shows that feeding natural anti-inflammatory agent and a synthetic NSAIDs singly or in combination with Synergy1 significantly reduced the incidence of AOM-induced ACF, with the group fed C + Synergy1 + curcumin having the greatest effect. The differences in the chemopreventive mechanisms can provide additive and synergistic efficacy, hence, adequate efficacy may be observed at lower and presumably less toxic doses of the individual agents.