Abstract

OBJECTIVE:

To investigate the chemopreventive effects of pioglitazone (exogenous PPAR gamma ligand) on rat colon aberrant crypt foci, a rat carcinogenesis model induced by dimethylhydrazine (DMH), and to compare pioglitazone with sulindac (a NSAID).

METHODS:

Thirty-two, 8-week-old, female Sprague-Dawley rats were randomly divided into four groups (n = 8 each). Group 1 rats were injected with DMH alone (120 mg.kg-1, single subcutaneous injection). Group 2 rats were injected with saline alone. Group 3 rats were pre-treated with sulindac (320 mg.kg-1) for 7 days before DMH initiation. Group 4 rats were treated with pioglitazone (100 mg.kg-1). The animals were killed at the end of the experiment (week 5) and the colons were stained with methylene blue. The aberrant crypt foci (ACF) of the colonic mucosa were assessed.

RESULTS:

In Group 1 rats (DMH only), the average numbers of ACF/colon and AC/colon were (182 +/- 93) and (263 +/- 198), respectively. In Group 2 (saline group) rats, no ACF were found. In Group 3 (sulindac group) rats, the average numbers of ACF/colon and AC/colon were (91 +/- 49) and (140 +/- 69), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). In Group 4 (pioglitazone group) rats, the average numbers of ACF/colon and AC/colon were (97 +/- 23) and (148 +/- 31), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). No difference was found in the values of Group 3 and Group 4.

CONCLUSION:

These results suggest that pioglitazone have chemopreventive effects against rat colon carcinogenesis induced by DMH, whose effect is similar to that of sulindac.