Research article

Pharmacokinetics and transcriptional effects of the anti-salmon lice drug emamectin benzoate in Atlantic salmon (Salmo salar L.)

Pål A Olsvik¹ , Kai K Lie¹ , Eva Mykkeltvedt¹ , Ole B Samuelsen² , Kjell Petersen³ , Anne-Kristin Stavrum^4,3 and Bjørn T Lunestad¹

¹  National Institute of Nutrition and Seafood Research, P.O. Box 2029 Nordnes, N-5817 Bergen, Norway

²  Institute of Marine Research, Fish Disease Group, P.O. Box 1870 Nordnes, 5817 Bergen, Norway

³  Computational Biology Unit, Bergen Center for Computational Science, University of Bergen, Thormøhlensgt 55, N-5008 Bergen, Norway

⁴  Department of Clinical Medicine, University of Bergen, N-5021 Bergen, Norway

author email corresponding author email

BMC Pharmacology 2008, 8:16doi:10.1186/1471-2210-8-16

Published:	11 September 2008

Abstract

Background

Emamectin benzoate (EB) is a dominating pharmaceutical drug used for the treatment and control of infections by sea lice (Lepeophtheirus salmonis) on Atlantic salmon (Salmo salar L). Fish with an initial mean weight of 132 g were experimentally medicated by a standard seven-day EB treatment, and the concentrations of drug in liver, muscle and skin were examined. To investigate how EB affects Atlantic salmon transcription in liver, tissues were assessed by microarray and qPCR at 7, 14 and 35 days after the initiation of medication.

Results

The pharmacokinetic examination revealed highest EB concentrations in all three tissues at day 14, seven days after the end of the medication period. Only modest effects were seen on the transcriptional levels in liver, with small fold-change alterations in transcription throughout the experimental period. Gene set enrichment analysis (GSEA) indicated that EB treatment induced oxidative stress at day 7 and inflammation at day 14. The qPCR examinations showed that medication by EB significantly increased the transcription of both HSP70 and glutathione-S-transferase (GST) in liver during a period of 35 days, compared to un-treated fish, possibly via activation of enzymes involved in phase II conjugation of metabolism in the liver.

Conclusion

This study has shown that a standard seven-day EB treatment has only a modest effect on the transcription of genes in liver of Atlantic salmon. Based on GSEA, the medication seems to have produced a temporary oxidative stress response that might have affected protein stability and folding, followed by a secondary inflammatory response.