Biological organisms are constantly challenged by xenobiotics and have evolved mechanisms to reduce, neutralize, or repair toxic outcomes. The various chemical defenses all utilize energy, but their specific costs and impacts on energy budgets are currently unknown. In this study, the energetic costs associated with the induction and substrate transport of the efflux transporter P-glycoprotein (P-gp [ABCB1, MDR1]) were examined in rainbow trout. An intraperitoneal injection of the P-gp inducer clotrimazole (0, 0.1, 1.0, and 10 mg/kg) increased P-gp activity (as measured by a competitive rhodamine 123 transport assay in hepatocytes) in a dose-dependent manner reaching a maximum induction of 2.8-fold. Maximum P-gp induction occurred at 50 h post-administration with the highest dose; significant induction of P-gp activity remained elevated over constitutive values until the last sampling time point (168 h). In vitro measurements of hepatocyte respiration indicated that basal P-gp activity transporting R123 as a substrate did not significantly increase respiration rates (range 18.0 to 23.2 ng O₂/min/10⁶ cells); however, following the induction of P-gp by clotrimazole and exposure to the P-gp substrate R123, respiration rates increased significantly (3.52-fold) over baseline values. Using whole animal respirometry, it was shown that respiration rates in fish exposed to R123 only or induced with clotrimazole were not different from controls (range 1.2 to 2.1 mg O₂/kg/min); however, respiration rates were significantly increased in fish with induced P-gp levels and also exposed to R123. This work indicates that basal and induced levels of P-gp activity do not incur significant energetic costs to fish; however, upon induction of P-gp and concomitant substrate exposures, energetic costs can increase and could pose challenges to organisms facing limited energy resources.

生物有机体不断受到异源生物的挑战，并已发展出减少，中和或修复毒性结果的机制。各种化学防御方法都利用能源，但是目前尚不清楚其具体成本和对能源预算的影响。在这项研究中，在虹鳟鱼中检查了与外排转运蛋白P-糖蛋白（P-gp [ABCB1，MDR1]）的诱导和底物转运相关的能量消耗。腹膜内注射P-gp诱导剂克霉唑（0、0.1、1.0和10 mg / kg）以剂量依赖性方式提高P-gp活性（通过竞争性若丹明123肝细胞中的竞争测定）诱导2.8倍。最高剂量的P-gp诱导发生在给药后50小时；直到最后一个采样时间点（168小时），P-gp活性的显着诱导仍高于组成值。肝细胞呼吸的体外测量表明，以R123为底物转运的基础P-gp活性不会显着提高呼吸速率（范围为18.0至23.2 ng O₂ / min / 10 ⁶格）；然而，在克霉唑诱导P-gp并暴露于P-gp底物R123之后，呼吸速率比基线值显着提高（3.52倍）。使用全动物呼吸测定法，表明仅暴露于R123或克霉唑诱导的鱼的呼吸速率与对照组无差异（1.2至2.1 mg O ₂/ kg / min）; 然而，诱导P-gp水平的鱼的呼吸速率显着增加，并且也暴露于R123。这项工作表明，P-gp活性的基础水平和诱导水平不会对鱼类产生大量的能量消耗。但是，在诱发P-gp以及随之而来的底物暴露后，高能成本可能会增加，并可能给面临能源有限的生物带来挑战。