• Aucun résultat trouvé

Introduction

Dans le document The DART-Europe E-theses Portal (Page 146-150)

Chapitre  I   :  Synthèse  Bibliographique

I. Introduction

Environmental pollution and its impact on inducing pernicious diseases have become major issues in public health and the preservation of biodiversity. There are many pollutants, with various structures and properties, that circulate in the air, soil and water and contaminate all the organisms in their ecosystems. The pollutants also flow through the contaminated organisms via the food chain, to man. Thus, environmental pollution may cause chronic toxicity in contaminated organisms, inducing ill health. Most pollutants reach rivers, lakes, aquifers and oceans through rainfall and runoff water.

Currently, aquatic pollution analysis is carried out mainly by environmental management services using physico-chemical measures or biological indicators such as diatoms or macro-invertebrates. However, these methods have many limitations. Indeed, some toxins, such as new drugs and their metabolites, which are not well documented, have not been detected by physico-chemical means. Very low concentrations of many such pollutants have not been monitored (Narbonne, 1998). Moreover, the pollution generally results from a cocktail of different pollutants in the natural environment. Therefore, their synergistic and/or antagonist effects cannot be identified by standard physico-chemical analyses (Dutka, 1998). Hence in recent years, the concept of biomonitoring has been increasingly developed. It is based on the

use of biomarkers to study the biological responses of organisms to pollutants (Lagadic et al., 1997).

Fish, particularly salmonids, are integrative organisms with regard to environmental conditions and water quality. Moreover, they are "bioaccumulation" organisms (Mortensen et al., 2011). This refers to the absorption and storage of various xenobiotics within living organisms, after long-term exposure to a contaminated environment. Salmonids, being predators, are at the top of the aquatic food chain. Thus they represent a suitable model for aquatic ecosystem analysis (Celander, 2011). Among the Salmonidae, Salmo trutta fario or brown trout, native to rivers and also fish-farmed, provide a ubiquitous and highly sensitive index of water quality.

The blood circulation is a hub for the trade and transport of a variety of physiological molecules and for passage and accumulation of xenobiotics (drugs and/or pollutants). The various pollutants are found either directly in the blood or in organs, tissues and cells, before being gradually released into the bloodstream. Erythrocytes comprise the major cellular component of the blood and in fish they are nucleated (Soldatov, 2005).

Multidrug Resistance (MDR) proteins have been described largely in cancer cells as membrane transporters involved in resistance to chemotherapy (Sarkadi et al., 2006). In reality, MDR membrane transporters belong to the ubiquitous, evolutionarily conserved family of the ATP-binding cassette (ABC) proteins. They are found in practically all living organisms from prokaryotes to eukaryotes (Bamdad et al., 1999; Bamdad et al., 1997;

Camarès O, 2004; Dudler and Sidler, 1998; Geisler et al., 2005; Gerlach et al., 1986;

Krogstad et al., 1992; Kurelec, 1992; Loncar et al., 2010; Sarkadi et al., 2006; Sturm et al., 2001; Vache et al., 2007; Vache et al., 2006; Zaja et al., 2007). MDR phenotype proteins are membrane detoxification pumps causing xenobiotics efflux from cells. They recognize varied molecules, including hydrophobic compounds, to amphipathic anions and cations, such as heavy metals and the majority of pharmaceutical drugs (Bamdad et al., 1999; Bamdad et al., 1997; Einicker-Lamas et al., 2003; Marquez B, 2011; Sarkadi et al., 2006; Vache et al., 2007;

Vache et al., 2006). Due to this property, MDR proteins are involved in natural defense mechanisms of cells, tissues and organs, and form an essential part of the innate defense system known as “chemo-immunity” (Sarkadi et al., 2006). In man, two major MDR proteins include members of the ABCB (ABCB1/MDR1/P-gp) and ABCG (ABCG2/Brest Cancer resistance Protein) sub-families (Natarajan et al., 2012; Sarkadi et al., 2006).

Figure   1.   Maps   showing   the   situation   of   the   three   natural   sampling   sites   in   Auvergne   -­‐

FRANCE  

A:  Location  of  Puy-­‐de-­‐Dôme  department  in  France  

B:  Location  of  the  three  sampling  sites.  Pink  fish  represent  the  sampling  site.    

C:   Location   of   “Vallée   de   Chaudefour”   site,   situated   in   a   nature   reserve,   free   from   human   activity.  

D:  Location  of  "Lomprat"  site,  situated  in  a  very  small  village  with  about  200  habitants,  free   from  any  industrial  activities.  

E:  Location  of  “Issoire”  site,  situated  in  the  center  of  the  town  of  “Issoire”,  which  is  a  very   small  industrial  town  with  12,000  inhabitants.  

Our previous studies have focused on the ABCB1/ P-gp expression mode in the ciliated freshwater protozoan Tetrahymena pyriformis (Bamdad et al., 1999; Bamdad et al., 1997;

Camarès O, 2004) and the vinegar fly Drosophila melanogaster after exposure to Polycyclic Aromatic Hydrocarbon (PAH) pollutants (Vache et al., 2007; Vache et al., 2006). In these experiments, carried out in lab and field, we demonstrated a dose-dependent response of ABCB1 /P-gp after exposure to increasing concentrations of various PAHs. The ABCB1/P-gp in Tetrahymena pyriformis and Drosophila melanogaster were induced in response to both aquatic and air contamination by different classes of PAHs.

MDR proteins being ubiquitous and inducible by various xenobiotics, they may prove to be an excellent tool to use as biomarkers. This study focused on the co-expression of two major MDR proteins, the ABCG2 protein and P-gp in the red blood cells of the brown trout. MDR biomarker development was carried out first in the laboratory by developing primary erythrocyte cultures. The MDR proteins response was analyzed in the primary erythrocyte culture after exposure to increasing concentrations of benzo-a-pyren (BaP), a highly toxic PAH model. Then, MDR protein used as a biomarker was tested in wild brown trout from different rivers.

Dans le document The DART-Europe E-theses Portal (Page 146-150)

Documents relatifs