Effect of emamectin benzoate on transcriptional expression of cytochromes P450 and the multidrug transporters (Pgp and MRP1) in rainbow trout ( Oncorhynchus mykiss) and the sea lice Caligus rogercresseyi

Abstract

Caligus rogercresseyi is a sea louse that affects salmon farming industry throughout the Southern hemisphere. In Chile, oral delivery of emamectin benzoate (EMB) to salmon was the main treatment used; however, C. rogercresseyi became resistant to EMB. The aims of this study were determine the effect of EMB on proteins involved in metabolism and drug resistance in rainbow trout ( Oncorhynchus mykiss) and C. rogercresseyi. Since no commercial antibodies are available for these salmon's proteins, the expression of trout cytochrome P450 CYP2K1, CYP2M1, CYP3A and CYP3A27, and the multidrug transporters Pgp and MRP1 were investigated by semi-quantitative duplex RT-PCR. Trout specimens infested with C. rogercresseyi were medicated with EMB by a standard seven-day oral treatment in salmon farms from southern Chile, and collected between 10 and 25 days after the completion of medication. The samples examined were liver, muscle, gill, middle kidney and intestine from control and EMB treated rainbow trout, and C. rogercresseyi's total homogenates. In trout tissues most CYP and MDR gene expressions were up-regulated by EMB treatment, being MRP1 mRNA in all tissues, but particularly in the kidney and intestine, and CYP2M1 mRNA from muscle and gill, the most augmented. CYP3A, CYP3A27, CYP2K1 and Pgp mRNAs were slightly affected in the most tissues analyzed. In C. rogercresseyi minimal up-regulation of the expression for most of mRNA analyzed was observed, except for CYP2M1 mRNA, decreasing its expression by half, and CYP3A27 doubling its expression levels. Nonetheless, CYP3A mRNA expression was not detected in this parasite. These results suggest that treatment with EMB in salmon regulates the transcriptional expression of proteins involved in metabolism, distribution and elimination of endobiotics and xenobiotics, such as hormones and drugs, and even could affect the pharmacokinetics of EMB in the same treatment.