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Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Authors :
Laetitia Knockaert
Alain Fautrel
Julie Pajaud
Catherine Ribault
Sylvie Lepage
Catherine Lucas-Clerc
Marie-Anne Robin
Alain Berson
Pierre-Emmanuel Prost
Bernard Fromenty
Jean-Marc Bégué
Foie, métabolismes et cancer
Université de Rennes 1 (UR1)
Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 )
Centre de recherche biomédicale Bichat-Beaujon (CRB3)
Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Service des explorations fonctionnelles
Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Laboratoire de biochimie générale
Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Université de Rennes (UR)-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 )
Service des explorations fonctionnelles [CHU Rennes]
CHU Pontchaillou [Rennes]
Le Corre, Morgane
Source :
Laboratory Investigation, Laboratory Investigation, Nature Publishing Group, 2012, 92 (3), pp.396-410. ⟨10.1038/labinvest.2011.193⟩, Laboratory Investigation, 2012, 92 (3), pp.396-410. ⟨10.1038/labinvest.2011.193⟩
Publication Year :
2011

Abstract

International audience; Although carbon tetrachloride (CCl(4))-induced acute and chronic hepatotoxicity have been extensively studied, little is known about the very early in vivo effects of this organic solvent on oxidative stress and mitochondrial function. In this study, mice were treated with CCl(4) (1.5 ml/kg ie 2.38 g/kg) and parameters related to liver damage, lipid peroxidation, stress/defense and mitochondria were studied 3 h later. Some CCl(4)-intoxicated mice were also pretreated with the cytochrome P450 2E1 inhibitor diethyldithiocarbamate or the antioxidants Trolox C and dehydroepiandrosterone. CCl(4) induced a moderate elevation of aminotransferases, swelling of centrilobular hepatocytes, lipid peroxidation, reduction of cytochrome P4502E1 mRNA levels and a massive increase in mRNA expression of heme oxygenase-1 and heat shock protein 70. Moreover, CCl(4) intoxication induced a severe decrease of mitochondrial respiratory chain complex IV activity, mitochondrial DNA depletion and damage as well as ultrastructural alterations. Whereas DDTC totally or partially prevented all these hepatic toxic events, both antioxidants protected only against liver lipid peroxidation and mitochondrial damage. Taken together, our results suggest that lipid peroxidation is primarily implicated in CCl(4)-induced early mitochondrial injury. However, lipid peroxidation-independent mechanisms seem to be involved in CCl(4)-induced early hepatocyte swelling and changes in expression of stress/defense-related genes. Antioxidant therapy may not be an efficient strategy to block early liver damage after CCl(4) intoxication.

Details

ISSN :
15300307 and 00236837
Volume :
92
Issue :
3
Database :
OpenAIRE
Journal :
Laboratory investigation; a journal of technical methods and pathology
Accession number :
edsair.doi.dedup.....b4fdf967a62086f6ea6193f1c16e9eb7
Full Text :
https://doi.org/10.1038/labinvest.2011.193⟩