No effect on adenoma formation in Min mice after moderate amount of flaxseed.

Abstract

The mammalian lignan enterolactone (ENL) produced from plant lignans, e. g. secoisolariciresinol diglycoside (SDG), may protect against various cancers in humans. The present work aims to evaluate the effect of flaxseed on tumour formation in multiple intestinal neoplasia (Min) mice, a model for colon tumorigenesis. Male and female Min mice were fed either with a non-fibre control diet or the same diet supplemented with 0.5 % (w/w) defatted flaxseed meal. Conversion of SDG to the mammalian lignans enterodiol (END) and ENL in the gut, and plasma ENL, were measured by HPLC with coulometric electrode array detector (CEAD) and timeresolved fluoroimmunoassay, respectively. Wild-type mice were also fed with the experimental diets in order to see whether lignan metabolism is different in Min and wild-type mice. The total number of adenomas or their size in the small intestine was not different in the flaxseed and control groups. The flaxseed group had a tendency for a decreased number of colon adenomas in both genders. Gender and genotype based differences were found in the intestinal ENL levels. When compared to Min females, Min males in the flaxseed group had several fold higher ENL levels in the small intestine (Min males 125 +/- 124.5 nmol/g vs. females 22.8 +/- 16.0 nmol/g, P = 0.048) and caecum (47.6 +/- 31.6 nmol/g vs. females 14.5 +/- 6.6 nmol/g, P = 0.001). Presence of adenomas in the gut influences the intestinal lignan metabolism. Min mice had less intestinal END and ENL as compared with the wild-type mice (P < 0.05). Mean plasma ENL increased 7-fold during the flaxseed feeding (7 nmol/L in control vs. 50 nmol/L in flaxseed group) but no differences between gender and genotype were found. The plasma ENL level did not correlate with adenoma number in the small intestine and colon. The number of intestinal adenomas in the Min mouse model is not related to ENL level in plasma nor is it associated with the levels of intestinal lignans. A gender difference in ENL lignan metabolism was found in the gut but not in the plasma.