1. Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine
- Author
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Sylvie Penet, Joëlle Dewulf, Bruno Pot, Christophe Carnoy, Kelly Le Clère, Thierry Chassat, Fabrice Nesslany, Lauren Nakab, Jérôme Breton, Mathieu Sauty, Benoît Foligné, Patrick Thomas, Catherine Daniel, Lactic Acid Bacteria & Mucosal Immunity - CIIL, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The present study was done in the context of a french multidisciplinary project called 'Mélodie-Reve' (Métaux lourds, désordres immunitaires et écotoxicologie intestinale—(bio)-Remédiation in vivo, standing for Heavy metals, immune disorders and intestinal Ecotoxicology—in vivo (bio)-remediation) supported by the National Research Agency (ANR-09-CES-016)., ANR-09-CESA-0016,MELODIE-REVE,Métaux Lourds, Désordres Immunitaires Ecotoxicologie Intestinale & (bio)- Remédiation in Vivo: Evaluation des impacts et traitements potentiels(2009), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Daniel, Catherine, Contaminants, Ecosystèmes et Santé - Métaux Lourds, Désordres Immunitaires Ecotoxicologie Intestinale & (bio)- Remédiation in Vivo: Evaluation des impacts et traitements potentiels - - MELODIE-REVE2009 - ANR-09-CESA-0016 - CESA - VALID, and Department of Bio-engineering Sciences
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Time Factors ,Bioavailability ,Metals, Heavy/administration & dosage ,Health, Toxicology and Mutagenesis ,[SDV]Life Sciences [q-bio] ,Gene Expression Regulation/drug effects ,010501 environmental sciences ,Pharmacology ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Intestinal absorption ,Mice ,Intestinal mucosa ,Cadmium Chloride ,Tissue Distribution ,Intestinal Mucosa ,0303 health sciences ,Gastrointestinal tract ,Mice, Inbred BALB C ,General Medicine ,6. Clean water ,3. Good health ,Gut Epithelium ,Intestine ,Intestines ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Lead/administration & dosage ,Female ,Cadmium Chloride/administration & dosage ,Cadmium ,Intestinal Mucosa/drug effects ,Biological Availability ,Ileum ,Biology ,Intestines/drug effects ,03 medical and health sciences ,Metals, Heavy ,medicine ,Animals ,030304 developmental biology ,0105 earth and related environmental sciences ,Gastrointestinal Tract/drug effects ,Dose-Response Relationship, Drug ,Small intestine ,Comet assay ,Gastrointestinal Tract ,Gene Expression Regulation ,Intestinal Absorption ,Lead ,DNA Damage/drug effects ,Immunology ,Mutagens/administration & dosage ,Gene expression ,Genotoxicity ,DNA Damage ,Mutagens - Abstract
International audience; Chronic ingestion of environmental heavy metals such as lead (Pb) and cadmium (Cd) causes various well-documented pathologies in specific target organs following their intestinal absorption and subsequent accumulation. However, little is known about the direct impact of the non-absorbed heavy metals on the small intestine and the colon homeostasis. The aim of our study was to compare the specific bioaccumulation and retention of Cd and Pb and their effect on the essential metal balance in primary organs, with those occurring specifically in the gastrointestinal tract of mice. Various doses of Cd (5, 20 and 100 mg l−1) and Pb (100 and 500 mg l−1) chloride salts were provided in drinking water for subchronic to chronic exposures (4, 8 and 12 weeks). In contrast to a clear dose- and time-dependent accumulation in target organs, results showed that intestines are poor accumulators for Cd and Pb. Notwithstanding, changes in gene expression of representative intestinal markers revealed that the transport-, oxidative- and inflammatory status of the gut epithelium of the duodenum, ileum and colon were specifically affected by both heavy metal species. Additionally, in vivo comet assay used to evaluate the impact of heavy metals on DNA damage showed clear genotoxic activities of Cd, on both the upper and distal parts of the gastrointestinal tract. Altogether, these results outline the resilience of the gut which balances the various effects of chronic Cd and Pb in the intestinal mucosa. Collectively, it provides useful information for the risk assessment of heavy metals in gut homeostasis and further disease’s susceptibility.
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- 2013