1. Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice
- Author
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Moana Gelu-Simeon, François Tiaho, Valentine Genet, Catherine Lucas-Clerc, Elise Tabet, Claire Piquet-Pellorce, Michel Samson, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], This work was supported by Inserm, Université de Rennes 1 and the ANR (Agence nationale de la recherche, Programme CESA 2011, Acronyme : Hepatochlor). For immunohistochemistry and animal house facilities, we would like to thank the dedicated platforms (i.e. H2P2 (Pascale Bellaud and Roselyne Viel), Arche (Laurence Bernard)) of SFR BIOSIT, University of Rennes 1, France., Jonchère, Laurent, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
- Subjects
0301 basic medicine ,CCl4 ,Male ,Insecticides ,Cirrhosis ,Time Factors ,010501 environmental sciences ,Toxicology ,Liver Cirrhosis, Experimental ,01 natural sciences ,chemistry.chemical_compound ,Fibrosis ,Carbon Tetrachloride ,education.field_of_study ,Extracellular Matrix Proteins ,[SDV.TOX.ECO] Life Sciences [q-bio]/Toxicology/Ecotoxicology ,biology ,Alanine Transaminase ,General Medicine ,3. Good health ,Kepone ,Liver ,Chlordecone ,Chemical and Drug Induced Liver Injury, Chronic ,Disease Progression ,Collagen ,[SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology ,Liver cancer ,medicine.medical_specialty ,Population ,digestive system ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Aspartate Aminotransferases ,education ,0105 earth and related environmental sciences ,business.industry ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,medicine.disease ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,digestive system diseases ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Alanine transaminase ,chemistry ,Gene Expression Regulation ,biology.protein ,Liver function ,Hepatic fibrosis ,business ,Biomarkers - Abstract
International audience; Chronic liver damage due to viral or chemical agents leads to a repair process resulting in hepatic fibrosis. Fibrosis may lead to cirrhosis, which may progress to liver cancer or a loss of liver function, with an associated risk of liver failure and death. Chlordecone is a chlorinated pesticide used in the 1990s. It is not itself hepatotoxic, but its metabolism in the liver triggers hepatomegaly and potentiates hepatotoxic agents. Chlordecone is now banned, but it persists in soil and water, resulting in an ongoing public health problem in the Caribbean area. We assessed the probable impact of chlordecone on the progression of liver fibrosis in the population of contaminated areas, by developing a mouse model of chronic co-exposure to chlordecone and a hepatotoxic agent, carbon tetrachloride (CCl4). After repeated administrations of chlordecone and CCl4 by gavage over a 12-week period, we checked for liver damage in the exposed mice, by determining serum liver transaminase (AST, ALT) levels, histological examinations of the liver and measuring the expression of genes encoding extracellular matrix components. The co-exposure of mice to CCl4 and chlordecone resulted in significant increases in ALT and AST levels. Chlordecone also increased expression of the Col1A2, MMP-2, TIMP-1 and PAI-1 genes in CCl4-treated mice. Finally, we demonstrated, by quantifying areas of collagen deposition and alpha-SMA gene expression, that chlordecone potentiated the hepatic fibrosis induced by CCl4. In conclusion, our data suggest that chlordecone potentiates hepatic fibrosis in mice with CCl4-induced chronic liver injury
- Published
- 2015