Inducibility and Nutritional Modulation of P-Glycoprotein Efflux Activity in Rainbow Trout Hepatocytes

P-glycoprotein (P-gp) is an ATP-dependent efflux transporter that contributes to cellular defense by exporting xenobiotics. While well characterized in mammals, its inducibility and physiological regulation in fish remain poorly understood. This study examined the functional induction of P-gp in juvenile rainbow trout (Oncorhynchus mykiss) hepatocytes following xenobiotic exposure and assessed how energy status (fed vs. fasted) influences both basal and inducible efflux activity. In vivo exposure to clotrimazole, dexamethasone, benzo[a]pyrene, and rifampicin significantly reduced rhodamine 123 (R123) accumulation in hepatocytes, indicating enhanced P-gp activity. Clotrimazole elicited the strongest response, with effects evident by day 3. Induction was dose-dependent and plateaued at doses ≥ 4 mg/kg. A single injection produced transient P-gp activity, while repeated exposures sustained efflux for 28 days. Fasting led to increased R123 accumulation, indicating suppressed basal P-gp function, though inducibility was retained but attenuated. These findings confirm that P-gp is inducible in trout and modulated by nutritional state. This functional plasticity has ecological relevance, as contaminant exposure during energetically limited periods (e.g., migration, overwintering) may compromise chemical defense. Understanding these trade-offs is key to assessing the resilience of wild fish to pollution stressors.