A possible involvement of acidic glycosaminoglycans in kanamycin ototoxicity.
The content of acidic glycosaminoglycans (AGAG) was determined quantitatively by electrophoretic microanalysis in the cochlea, kidney and brain of the guinea pig. Kanamycin treatment (400 mg/kg body weight/day, i.m., 10 successive days) reduced the content of AGAG markedly in the lateral wall of the membranous cochlea. Furthermore, from the results of the ultrahistochemical and freeze-fracturing study, we propose here an "excretion system for basic aminoglycoside antibiotics" by means of the co-operation of spiral ligament cells and AGAG produced by them. Thus we have tentatively concluded both that kanamycin is excreted via the above mentioned "excretion system" in the lateral wall of the membranous cochlea and that it damages this system to form the circulus vitiosus of its opopoxicity.
D000818:Animals; D001489:Basilar Membrane / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003094:Collagen; D005614:Freeze Fracturing; D006025:Glycosaminoglycans / Q000378:metabolism*; D006168:Guinea Pigs; D007612:Kanamycin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D013137:Spiral Lamina / Q000648:ultrastructure; D013316:Stria Vascularis / Q000648:ultrastructure
D006025:Glycosaminoglycans; D007612:Kanamycin; D003094:Collagen