Reprod. Nutr. Dev. 43 (2003) 347-356
DOI: 10.1051/rnd:2003028

Fructooligosaccharide associated with celecoxib reduces the number of aberrant crypt foci in the colon of rats

Bruno Buecher^a, Cécile Thouminot^a, Jean Menanteau^b, Christian Bonnet^c, Anne Jarry^a, Marie-Françoise Heymann^a, Christine Cherbut^c, Jean-Paul Galmiche^a and Hervé M. Blottière<sup>a, c, d

a</sup>  Centre de Recherche en Nutrition Humaine de Nantes, INSERM U539, CHU Hôtel-Dieu, 44035 Nantes, France
^b  Centre de Recherche en Nutrition Humaine de Nantes, INSERM U419, CHU Hôtel-Dieu, 44035 Nantes, France
^c  Centre de Recherche en Nutrition Humaine de Nantes, INRA-UFDNH, CHU Hôtel-Dieu, 44035 Nantes, France
^d  Present address: UNSA-INRA, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France

(Received 24 March 2003; accepted 24 June 2003)

Abstract
According to Burkitt's hypothesis, dietary fibres may protect against the development of colorectal cancer. In rats, studies have shown that only butyrate-producing fibres are protective. In parallel, in humans, non-steroidal anti-inflammatory drugs, which target cyclooxygenases, have been shown to display a protective effect against colorectal cancer. Among them, COX-2-selective inhibitors which present less side effects than non-selective agents, are promising as chemopreventive agents. Our aim was to analyse the effect of an association between butyrate-producing fibres and the COX-2 inhibitor on the development of aberrant crypt foci (ACF) in rats. Fisher F344 rats were fed with (1) a standard low fibre control diet; (2) the standard diet supplemented with 1500 ppm celecoxib; (3) a diet supplemented with 6% fructo-oligosaccharide (FOS); and (4) a diet with both celecoxib and FOS. Three weeks later, the rats were injected twice with azoxymethane and the number of ACF was determined 15 weeks later. In the control group, ACF were found. This number was not significantly modified by the addition of FOS or celecoxib alone to the diet. However, the association of FOS and celecoxib resulted in a 61% reduction in the number of ACF ( P < 0.01). The number of aberrant crypt per foci was also reduced. Thus, although no significant effect of celecoxib or FOS alone was identified, the association of butyrate-producing fibre and celecoxib was effective in preventing the development of ACF. This preliminary study argues for a strong protective effect of such an association which deserves further studies.

Key words: COX-2 / butyrate / colorectal cancer / NSAID

Correspondence and reprints: Hervé M. Blottière hblot@jouy.inra.fr

© INRA, EDP Sciences 2003