DISTRIBUTION OF GENTAMICIN TO THE COCHLEA OF THE CHICKEN-EMBRYO

Aminoglycoside antibiotics are ototoxic in mammals and birds, includin g recently hatched chicks, but chicken embryos are insensitive to the ototoxicity of gentamicin, kanamycin, and streptomycin. To determine w hether or not the insensitivity is due to a lack of antibiotic distrib ution to the avian cochlea, the distribution of gentamicin to the coch lea of the White Leghorn chicken embryo was compared to the distributi on to the cochlea of the recently hatched White Leghorn chick. Fertile eggs were injected with a maximally tolerated dose of gentamicin sulf ate (0.1 mg/egg/day) on incubation days 10-18, and the chicks were inj ected subcutaneously with either 5 mg (non-ototoxic) or 100 mg (ototox ic) gentamicin sulfate/kg body weight on days 1-9 after hatching. Gent amicin sulfate was histochemically detected within the basilar papilla (the avian equivalent of the organ of Corti) in all treated chicken e mbryos and chicks by 1 day after the first injection, and the staining was intense after 3 days of treatment. By ultrastructural immunocytoc hemistry, mild, diffuse labeling for gentamicin sulfate was detected w ithin the endoplasmic reticulum of short and tall hair cells of chicke n embryos by incubation day 17. Moderate labeling of gentamicin sulfat e was detected in the infracuticular region of lysosomes of hair cells in chicks receiving 5 treatments of gentamicin sulfate at 5.0 mg/kg b ody weight and after 1 treatment of gentamicin sulfate at 100 mg/kg bo dy weight. There was labeling of phosphatidylinositol 4,5-bisphosphate (PIP2), believed to be an essential factor in the ototoxicity of gent amicin in the stereocilia, cuticular plate, nucleus, endoplasmic retic ulum, cell walls, and tight junctions of hair cells in all control and treated chicken embryos and hatched chicks at each time point with li ttle variation in the amount. In hatched chicks from the high-dose gro up, short and tall hair cell loss was detected after 3 doses of gentam icin sulfate, and degeneration of dark cells in the tegmentum vasculos um was observed after 5 doses. No hair cell loss and no ultrastructura l evidence of degeneration, accumulation of gentamicin sulfate, or an increase in the numbers of lysosomes were detected in hair cells from chicken embryos. Although there was no evidence of drug-induced ototox icity, PIP, and gentamicin were detected in the hair cells from chicke n embryos. Therefore, the intracellular concentration of gentamicin wa s either insufficient to induce toxicity or the hair cells were still functionally undeveloped and could not be affected by the gentamicin.