Olsvik Pål A, Lie Kai K, Mykkeltvedt Eva, Samuelsen Ole B, Petersen Kjell, Stavrum Anne-Kristin, Lunestad Bjørn T
National Institute of Nutrition and Seafood Research, P,O, Box 2029 Nordnes, N-5817 Bergen, Norway.
BMC Pharmacol. 2008 Sep 11;8:16. doi: 10.1186/1471-2210-8-16.
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.
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.
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.
甲氨基阿维菌素苯甲酸盐(EB)是用于治疗和控制大西洋鲑鱼(Salmo salar L)感染海虱(Lepeophtheirus salmonis)的主要药物。初始平均体重为132克的鱼通过标准的七天EB处理进行实验性给药,并检测肝脏、肌肉和皮肤中的药物浓度。为了研究EB如何影响大西洋鲑鱼肝脏中的转录,在给药开始后的第7、14和35天通过微阵列和定量聚合酶链反应(qPCR)对组织进行评估。
药代动力学检查显示,在给药期结束七天后的第14天,所有三个组织中的EB浓度最高。在肝脏转录水平上仅观察到适度影响,在整个实验期间转录的倍数变化较小。基因集富集分析(GSEA)表明,EB处理在第7天诱导氧化应激,在第14天诱导炎症。qPCR检查表明,与未处理的鱼相比,在35天的时间里,EB给药显著增加了肝脏中热休克蛋白70(HSP70)和谷胱甘肽-S-转移酶(GST)的转录,可能是通过激活肝脏中参与代谢II期结合的酶。
本研究表明,标准的七天EB处理对大西洋鲑鱼肝脏中的基因转录只有适度影响。基于GSEA,该药物似乎产生了一种可能影响蛋白质稳定性和折叠的临时氧化应激反应,随后是继发性炎症反应。