TY - JOUR
T1 - A systemic gentamicin pathway across the stria vascularis
AU - Dai, Chun Fu
AU - Steyger, Peter S.
N1 - Funding Information:
The authors thank Dennis Trune for insightful discussions on the manuscript, and Qi Wang for her assistance with image analysis. Funded by DC 04555 (PSS), and P30 DC 05983 grants from the National Institute of Communication and other Disorders, NIH; China Scholarship Council (No. 20361037) and the Educational Ministry of China grant NCET 06-0369 (CFD).
PY - 2008/1
Y1 - 2008/1
N2 - The mechanism(s) by which systemically-administered aminoglycosides enter the cochlea remain poorly understood. To elucidate which mechanisms may be involved, we co-administered different molar ratios of gentamicin and fluorescent gentamicin (GTTR) to mice in three different regimens: (1) gentamicin (150, 300 or 600 mg/kg) containing a constant 300:1 molar ratio of gentamicin:GTTR; (2) 300 mg/kg gentamicin containing a variable molar ratio of gentamicin:GTTR (150:1-600:1), or (3) an increasing dose of gentamicin (150-900 mg/kg), each dose containing 1.7 mg/kg GTTR. Three hours later, cochleae were fixed and examined by confocal microscopy. First, increasing doses of a constant molar ratio of gentamicin:GTTR, resulted in increasing intensities of GTTR fluorescence in hair cells and strial tissues. Second, a fixed gentamicin dose with increasing molar dilution of GTTR led to decreasing GTTR fluorescence in hair cells and strial tissues. Third, a fixed GTTR dose with increasing molar dilution by gentamicin led to decreased GTTR uptake in hair cells and marginal cells, but not intra-strial tissues and capillaries. Thus, only hair cell and marginal cell uptake of GTTR is competitively inhibited by gentamicin, suggesting that a regulatable barrier for gentamicin entry into endolymph exists at the interface between marginal cells, the intra-strial space and intermediate cells.
AB - The mechanism(s) by which systemically-administered aminoglycosides enter the cochlea remain poorly understood. To elucidate which mechanisms may be involved, we co-administered different molar ratios of gentamicin and fluorescent gentamicin (GTTR) to mice in three different regimens: (1) gentamicin (150, 300 or 600 mg/kg) containing a constant 300:1 molar ratio of gentamicin:GTTR; (2) 300 mg/kg gentamicin containing a variable molar ratio of gentamicin:GTTR (150:1-600:1), or (3) an increasing dose of gentamicin (150-900 mg/kg), each dose containing 1.7 mg/kg GTTR. Three hours later, cochleae were fixed and examined by confocal microscopy. First, increasing doses of a constant molar ratio of gentamicin:GTTR, resulted in increasing intensities of GTTR fluorescence in hair cells and strial tissues. Second, a fixed gentamicin dose with increasing molar dilution of GTTR led to decreasing GTTR fluorescence in hair cells and strial tissues. Third, a fixed GTTR dose with increasing molar dilution by gentamicin led to decreased GTTR uptake in hair cells and marginal cells, but not intra-strial tissues and capillaries. Thus, only hair cell and marginal cell uptake of GTTR is competitively inhibited by gentamicin, suggesting that a regulatable barrier for gentamicin entry into endolymph exists at the interface between marginal cells, the intra-strial space and intermediate cells.
UR - http://www.scopus.com/inward/record.url?scp=37549053577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37549053577&partnerID=8YFLogxK
U2 - 10.1016/j.heares.2007.10.010
DO - 10.1016/j.heares.2007.10.010
M3 - Article
C2 - 18082985
AN - SCOPUS:37549053577
VL - 235
SP - 114
EP - 124
JO - Hearing Research
JF - Hearing Research
SN - 0378-5955
IS - 1-2
ER -