This study investigated the effect of short
curcumin treatment, a natural
antioxidant on
1,2-dimethylhydrazine (
DMH)-induced
aberrant crypt foci (ACF) in mice. The incidence of
aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first
DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in
malondialdehyde vs. 36% decrease in GSH.
DMH also increased inducible nitric synthase (iNOS)
mRNA transcripts (250%),
nitrites level (240%) and
arginase activity (296%), leading to nitrosative stress and cell proliferation.
Curcumin treatment, starting at week 10 post-
DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and
arginase activity (73%), and improved redox status by approximately 46%, compared to
DMH-treated mice. Moreover,
curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly,
curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of
curcumin was driven by the reduction of
arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by
curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of
curcumin.