Modulation of doxorubicin concentration by cyclosporin A in brain and testicular barrier tissues expressing P-glycoprotein in rats

摘要: P-glycoprotein (Pgp) is an inducible transmembrane protein that functions as ATP-dependent efflux pump. Pgp normally expressed in two types of cells: specialized epithelial cells with secretory/excretory (e.g., proximal renal tubules) and endothelial the capillary blood-brain barrier). In normal tissues, could exert a cytoprotective effect by facilitating excretion drugs. It follows inhibition would alter pharmacokinetics drugs, like doxorubicin, express Pgp. The purpose this study was to determine whether or not cyclosporin A (CsA) facilitated transport certain drugs across blood tissue barriers brain testes (barriers tissues expressing Pgp). 120 retired male breeder CD Fisher rats were randomly assigned groups 4 each. They given either CsA, CsA vehicle, saline followed doxorubicin (Dox), cisplatin (CDDP), Evan's blue (EB), sodium fluorescein (NaF), horseradish peroxidase (HRP). There dose dependent increase concentration testes, but platinum (Pt) concentrations, derived from CDDP, unaffected. Unlike Dox, can be effluxed These increases Dox concentrations due altered vascular permeability result treatment determined lack EB, NaF, HRP parenchyma. Modulation function may prove useful for improving chemotherapy efficacy patients malignancies affecting blood-tissue barriers.