P-glycoprotein (P-gp) is a membrane-bound transporter encoded by Mdr1a/Abcb1a and Mdr1b/Abcb1b genes in rodents involved in the efflux of cytotoxic chemicals and metabolites from cells. Modulation of its activity influences P-gp-mediated drug delivery and drug-drug interaction (DDI). In the current study, we tested the effects of fenofibrate on P-gp mRNA and protein content in non-obese model of metabolic syndrome. Males hereditary hypertriglyceridemic rats (HHTg) were fed standard laboratory diet (STD) (Controls) supplemented with micronized fenofibrate in lower (25 mg/kg b. wt./day) or in higher (100 mg/kg b. wt./day) dose for 4 weeks. Liver was used for the subsequent mRNA and protein content analysis. Fenofibrate in lower dose decreased hepatic Mdr1a by 75% and Mdr1b by 85%, while fenofibrate in higher dose decreased Mdr1a by 90% and Mdr1b by 92%. P-gp protein content in the liver was decreased by 74% in rat treated with fenofibrate at lower dose and by 88% in rats using fenofibrate at higher dose. These findings demonstrate for the first time that fenofibrate decreases both mRNA and protein amount of P-gp and suggest that fenofibrate could affect bioavailability and interaction of drugs used to treat dyslipidemia-induced metabolic disorders.

Center of Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czechia

Department of Pharmacology Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc Czechia

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc Czechia

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