Differential effects of gentamicin on the distribution of cochlear function in albino and pigmented guinea pigs.
It has been suggested that the high affinity of melanin pigment for aminoglycoside antibiotics may cause these drugs to bind preferentially to the pigmented inner ear, producing greater ototoxicity than in the amelanotic albino cochlea. However, evidence of greater ototoxicity in albinos has led to the hypothesis that melanin inhibits the toxicity of these drugs in the pigmented inner ear. On the other hand, ototoxicity in the pigmented animals may simply be delayed relative to the albinos, only to become equal or even more severe with time. The present study was conducted to determine whether a relatively low dose of gentamicin (68.5 mg/kg) would produce differential ototoxicity between albino and pigmented guinea pigs which would persist long after drug exposure had stopped. Nine pigmented and eight albino guinea pigs were given gentamicin sulfate for 14 consecutive days, and were then allowed a two-month recovery period before cochlear analysis; 11 pairs of saline-injected or untreated albino and pigmented guinea pigs served as controls. The results showed that the gentamicin-treated albinos had significantly elevated thresholds for the compound action potential from the auditory nerve (CAP), and significantly lower endocochlear potentials (EP) and cochlear microphonic (CM) input-output voltage functions when compared to their respective controls, or to either group of pigmented guinea pigs. The CAP in drug-treated pigmented animals did not differ significantly from controls, and the differences in EP and CM were marginally significant. The results indicate that the pigmented cochlea is less susceptible to gentamicin than the albino cochlea, and support the hypothesis that melanin may inhibit aminoglycoside ototoxicity in the pigmented inner ear.
Conlee
J W
JW
VA Medical Center, Salt Lake City, UT 84148, USA.
Bennett
M L
ML
Creel
D J
DJ
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000417:Albinism / Q000503:physiopathology*; D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D003055:Cochlear Microphonic Potentials; D005839:Gentamicins / Q000633:toxicity*; D006168:Guinea Pigs; D008543:Melanins / Q000502:physiology; D000159:Vestibulocochlear Nerve / Q000187:drug effects / Q000503:physiopathology
D005839:Gentamicins; D008543:Melanins