ZFIN ID: ZDB-PUB-141007-2
ABCB1 and ABCC4 efflux transporters are involved in methyl parathion detoxification in ZFL cells
Nornberg, B.F., Batista, C.R., Almeida, D.V., Trindade, G.S., Marins, L.F.
Date: 2015
Source: Toxicology in vitro : an international journal published in association with BIBRA   29(1): 204-10 (Journal)
Registered Authors: Almeida, Daniela Volcan, Marins, Luis Fernando, Nornberg, Bruna Felix
Keywords: ABC transporters, Methyl parathion, Multixenobiotic resistance (MXR), Verapamil
MeSH Terms:
  • Animals
  • Cell Line
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Liver/metabolism*
  • Liver/physiology
  • Methyl Parathion/metabolism*
  • Multidrug Resistance-Associated Proteins/metabolism
  • Multidrug Resistance-Associated Proteins/physiology*
  • Real-Time Polymerase Chain Reaction
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed: 25286004 Full text @ Toxicol. In Vitro
ABSTRACT
The multi-xenobiotics resistance (MXR) mechanisms are the first line of defense against toxic substances in aquatic organisms and present great importance in the adaptation related to contaminated environments. Methyl parathion (MP) is a widely used organophosphate pesticide, which has been associated to various toxic effects in organisms. In the present work, we studied the main genes related to efflux transporters in zebrafish liver (ZFL) cells exposed to MP with and without an inhibitor of ABC transporters (verapamil). The results concerning transporters activity showed that the MXR mechanism is activated to detoxify from methyl parathion. The toxic effects of MP on ZFL cells were increased in the presence of the efflux transporter inhibitor, once cell viability was significantly decreased in co-exposure experiments. The combined exposure to MP and the inhibitor caused an increase in gene expression of P-gp1 (Abcb1) and MRP4 (Abcc4), suggesting that these transporters isoforms are associated with MP efflux. In general, the expression of genes related to the antioxidant defense system (ADS) was significantly increased in ZFL cells co-exposed to MP and verapamil. These data provide useful insights for better understanding of MP detoxification mechanism in fish hepatocytes.
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