Polyphenol-rich Marie Ménard apples and a low fat diet reduce 1,2-dimethylhydrazine induced colon carcinogenesis in rats: effects on inflammation and apoptosis.

Marie Ménard apples (MM), rich in polyphenols, show anti-inflammatory effects [1]. Since inflammation is a driving force in colon carcinogenesis, MM could have chemopreventive activity. Likewise, diets promoting carcinogenesis such as high-fat (HF) diets, may act increasing inflammation. Accordingly, 1,2-dimethylhydrazine (DMH)-induced rats were fed an HF diet; an HF diet containing lyophilized MM (AD group); a low–fat (LF) diet and a HF diet with piroxicam (PXC). Mucin depleted foci (MDF), precancerous lesions in the colon [2], were reduced in AD, LF and PXC groups compared with HF. Apoptosis in MDF of AD and LF-fed rats was significantly higher than in HF-fed rats. Peritoneal macrophage activation was decreased in AD, LF and PXC groups compared with HF, while plasmatic PGE2 was lower in the AD, but not in the LF group. Positive cells for CD68, a macrophage marker, were reduced in the colon of AD but not varied in LF or PXC groups. By RT-qPCR we showed a down regulation of TNFα, iNOS, IL1β, IL6 in the AD, but not in the LF group. In conclusion, MM had a strong chemopreventive effect reducing inflammation and increasing apoptosis in MDF, while the chemopreventive effect of LF seems mediated mainly by apoptosis in MDF.