Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats.
The end products of polyunsaturated fatty acid (PUFA) peroxidation, such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and isoprostanes (8-iso-PGF2α), 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 ω-6- vs. ω-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-PGF2α 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.
UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France. Electronic address: fgueraud@toulouse.inra.fr.
Françoise
F
Guéraud
UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.
Sylviane
S
Taché
CarMeN Unit, INSERM U1060/INRA 1235/University-Lyon1/INSA-Lyon, Team 3 "Glucolipotoxicity, Metabolic Stress and Diabetes," Faculté de Médecine Lyon Sud, BP 12, 165 Chemin du Grand Revoyet, 69921 Oullins Cedex, France.
Jean-Paul
JP
Steghens
Rudjer Boskovic Institute, Laboratory for Oxidative Stress, Bijenicka 54, HR-10000 Zagreb, Croatia.
Lidija
L
Milkovic
Rudjer Boskovic Institute, Laboratory for Oxidative Stress, Bijenicka 54, HR-10000 Zagreb, Croatia.
Suzana
S
Borovic-Sunjic
Rudjer Boskovic Institute, Laboratory for Oxidative Stress, Bijenicka 54, HR-10000 Zagreb, Croatia.
Neven
N
Zarkovic
UMR 1331 Toxalim, INRA, INP, UPS, Team 4 "Neuro-Gastroenterology and Nutrition" and Team 11 "Intestinal Development, Xenobiotics and ImmunoToxicology," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.
Eric
E
Gaultier
UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.
Nathalie
N
Naud
UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.
Cécile
C
Héliès-Toussaint
UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.
Fabrice
F
Pierre
UMR 1331 Toxalim, INRA, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food," BP 93173, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.
Nathalie
N
Priymenko
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000652:urine*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004032:Diet / Q000009:adverse effects*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects*; D005260:Female; D006418:Heme / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D012004:Rectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
D000975:Antioxidants; D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D006418:Heme; D008315:Malondialdehyde; D007501:Iron
4-Hydroxynonenal; Biomarkers; Colorectal cancer; Heme iron; Lipid peroxidation; Malondialdehyde; Polyunsaturated fatty acids