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Uptake of amikacin by hair cells of the guinea pig cochlea and vestibule and ototoxicity: Comparison with gentamicin
Institution:1. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran;2. Physiology-pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran;1. Department of Intensive Care Medicine, The Royal Brisbane and Women''s Hospital, Brisbane, Queensland, Australia;2. Department of Anaesthesia and Critical Care, University Hospital Birmingham, Birmingham, UK;3. Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia;1. Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Avenida Brasil, 4365, Rio de Janeiro, RJ, Brazil;2. Laboratório de Imunofarmacologia, Instituto Biomédico, Universidade Federal do Estado do Rio de Janeiro, Unirio, Brazil;3. Instituto de Inmunología Clínica y Experimental de Rosario (IDICER-CONICET UNR), 2000, Rosario, Argentina;4. Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Avenida Brasil, 4365, Rio de Janeiro, RJ, Brazil
Abstract:The distribution of amikacin (AK), an exclusive cochleo-toxic aminoglycosidic antibiotic (AA), and of gentamicin (GM), which is both cochleo- and vestibulo-toxic, has been studied in cochlear and vestibular hair cells. Guinea pigs were treated during six days with one daily injection of AK (450 mg/kg/day) or GM (60 mg/kg/day). AAs were detected, using immunocytochemical technique with scanning laser confocal microscopy, in isolated cells from guinea pigs sacrificed from 2 to 30 days after the end of the treatments. Results demonstrate a rapid uptake (as soon as after 2-day treatment) of both AAs by cochlear and vestibular hair cells and a very slow clearance. Particularly GM and AK are detected in type I and type II hair cells of the utricles and cristae ampullaris. The presence of these two molecules with different toxic potentialities towards cochlear and vestibular hair cells indicates that the selective ototoxicity of aminoglycosides cannot be explained simply on the basis of particular uptake and accumulation in the different sensory hair cells.
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