Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats

Françoise Guéraud (1) , Sylviane Taché (2) , J. P. Steghens (3) , L. Milkovic (4) , S. Borovic-Sunjic (4) , N. Zarkovic (4) , Eric Gaultier (5) , Nathalie Naud (1) , Cécile Héliès-Toussaint (1) , F. Pierre (1) , Nathalie Priymenko (1)

1 ToxAlim-PPCA - Prévention et promotion de la cancérogénèse par les aliments
2 ToxAlim - ToxAlim
3 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
4 Rudjer Boskovic Institute [Zagreb]
5 ToxAlim-ENTeRisk - Endocrinologie & Toxicologie de la Barrière Intestinale

The end products of polyunsaturated fatty acid (PUFA) peroxidation, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and isoprostanes (8-iso-PGF2alpha), are widely used as systemic lipid oxidation/oxidative stress biomarkers. However, some of these compounds have also a dietary origin. Thus, replacing dietary saturated fat by PUFAs would improve health but could also increase the formation of such compounds, especially in the case of a pro-oxidant/antioxidant imbalanced diet. Hence, the possible impact of dietary fatty acids and pro-oxidant compounds was studied in rats given diets allowing comparison of the effects of heme iron vs. ferric citrate and of omega-6- vs. omega-3-rich oil on the level of lipid peroxidation/oxidative stress biomarkers. Rats given a heme iron-rich diet without PUFA were used as controls. The results obtained have shown that MDA and the major urinary metabolite of HNE (the mercapturic acid of dihydroxynonane, DHN-MA) were highly dependent on the dietary factors tested, while 8-iso-PGF2alpha was modestly but significantly affected. Intestinal inflammation and tissue fatty acid composition were checked in parallel and could only explain the differences we observed to a limited extent. Thus, the differences in biomarkers were attributed to the formation of lipid oxidation compounds in food or during digestion, their intestinal absorption, and their excretion into urine. Moreover, fecal extracts from the rats fed the heme iron or fish oil diets were highly toxic for immortalized mouse colon cells. Such toxicity can eventually lead to promotion of colorectal carcinogenesis, supporting the epidemiological findings between red meat intake and colorectal cancer risk. Therefore, the analysis of these biomarkers of lipid peroxidation/oxidative stress in urine should be used with caution when dietary factors are not well controlled, while control of their possible dietary intake is needed also because of their pro-inflammatory, toxic, and even cocarcinogenic effects.

Mots clés: Female; Animals; Mice; Rats; Reactive Oxygen Species/metabolism; *Oxidative Stress; Antioxidants/metabolism; Biomarkers/*urine; Colon/drug effects/metabolism/*pathology; Colonic Neoplasms/etiology/metabolism/*pathology; Diet/*adverse effects; Fatty Acids; Unsaturated/*adverse effects; Heme/*metabolism; Iron/*metabolism; Lipid Peroxidation/drug effects; Malondialdehyde/metabolism; Inbred F344; Rectal Neoplasms/etiology/metabolism/pathology; Thiobarbituric Acid Reactive Substances/metabolism; Tumor Cells; Cultured; Tumor Microenvironment

Domaines: Sciences du Vivant [q-bio]

Françoise Guéraud, Sylviane Taché, J. P. Steghens, L. Milkovic, S. Borovic-Sunjic, et al.. Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats. Free Radical Biology and Medicine, 2015, 83, pp.192-200. ⟨10.1016/j.freeradbiomed.2015.02.023⟩. ⟨hal-01850558⟩