title: Systemic aminoglycosides are trafficked via endolymph into cochlear hair cells.
abstract: Aminoglycoside antibiotics rapidly enter and kill cochlear hair cells via apical mechanoelectrical transduction (MET) channels in vitro. In vivo, it remains unknown whether systemically-administered aminoglycosides cross the blood-labyrinth barrier into endolymph and enter hair cells. Here we show, for the first time, that systemic aminoglycosides are trafficked across the blood-endolymph barrier and preferentially enter hair cells across their apical membranes. This trafficking route is predominant compared to uptake via hair cell basolateral membranes during perilymph infusion.
authors.affiliation: Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.forename: Peter S
authors.initials: PS
authors.lastname: Steyger
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001693:Biological Transport, Active; D004710:Endolymph / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010498:Perilymph / Q000378:metabolism; D014966:Xanthenes
chemical_list: D000617:Aminoglycosides; D005456:Fluorescent Dyes; D005839:Gentamicins; D014966:Xanthenes; C034657:Texas red