The potentiation of ototoxicity when aminooxyacetic acid and kanamycin are co-administered.
Aminooxyacetic acid (AOAA) has been shown to confer protection against noise-induced cochlear trauma [3]. We, therefore, decided to study the possible protective effect of AOAA against kanamycin (KM) ototoxicity and found, instead, that AOAA potentiated the toxicity. To produce ototoxicity in guinea pigs, KM is usually given in 10-14 daily doses of 400 mg/kg s.c. However, when combined with a single dose of AOAA (8, 11, 15, or 25 mg/kg) a single 400 mg/kg dose of KM is sufficient to cause cochlear damage. Such animals show a negative Preyer's reflex between 1 to 3 days post injection. 21 days later hearing thresholds as detected electrocochleographically at 2, 4, 8, 12 and 16 kHz have changed drastically sometimes to the point of being undetectable. The damage seen histologically at this time is destruction of both inner and outer hair cells. A pharmacokinetic analysis of this potentiation revealed a slight prolongation of KM's sojourn in the inner ear. The possible mechanisms of this unexpected, marked potentiation are discussed but remain unknown.
D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D003051:Cochlea / Q000187:drug effects*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004357:Drug Synergism; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D034381:Hearing Loss / Q000139:chemically induced; D007612:Kanamycin / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D000085:Acetates; D000625:Aminooxyacetic Acid; D007612:Kanamycin