Marie Ménard apples with high polyphenol content and a low-fat diet reduce 1,2-dimethylhydrazine-induced colon carcinogenesis in rats: effects on inflammation and apoptosis.
Inflammation may increase cancer risk, therefore, we studied whether polyphenol-rich Marie Ménard (MM) apples with reported anti-inflammatory activity prevent 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats and, likewise whether high-fat (HF) diet promoting carcinogenesis, may affect inflammation. DMH-induced rats were fed for 15 weeks with: an HF diet (23% corn oil w/w); an HF diet containing 7.6% w/w lyophilized MM (apple diet (AD)); a low-fat (LF) diet and an HF diet containing piroxicam (PXC) (0.01% w/w) as control. Mucin depleted foci (MDF), precancerous lesions in the colon, were dramatically reduced in the AD, LF, and PXC groups compared with the HF. Peritoneal macrophage activation, an index of systemic inflammation, was significantly decreased in the AD, LF, and PXC groups. TNF-α, iNOS, IL-1β, IL-6 m-RNA expression in the colon, as well as CD68 cells and plasmatic PGE2 were lower in the AD, but not in the LF group. Apoptosis in the MDF of both the AD and LF-fed rats was significantly higher than in HF rats. In conclusion, AD has a strong chemopreventive effect, reducing inflammation, and increasing apoptosis, while the chemopreventive effect of the LF diet seems mediated mainly by increased apoptosis in MDF.
Department of Pharmacology, University of Florence, Florence, Italy.
Angelo Pietro
AP
Femia
Cristina
C
Luceri
Francesca
F
Bianchini
Maddalena
M
Salvadori
Francesca
F
Salvianti
Pamela
P
Pinzani
Piero
P
Dolara
Lido
L
Calorini
Giovanna
G
Caderni
D019813:1,2-Dimethylhydrazine / Q000009:adverse effects; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D018752:Diet, Fat-Restricted; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D027845:Malus / Q000737:chemistry*; D059808:Polyphenols / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000890:Anti-Infective Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D059808:Polyphenols; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha; D019813:1,2-Dimethylhydrazine