Differential susceptibility to gentamicin ototoxicity between albino and pigmented guinea pigs.
The known chemical affinity of melanin pigment for aminoglycoside antibiotics has led to the suggestion that higher concentrations of these drugs will bind to the pigmented inner ear and produce greater ototoxicity compared to the nonpigmented albino cochlea. Although this has provided a compelling hypothesis, results from the few investigations to address this question have been equivocal. In the present study, cochlear microphonic (CM) thresholds were recorded from albino and pigmented guinea pigs both before and two weeks after exposure for 14 consecutive days to 100 mg/Kg gentamicin. Cochleae were dissected and half-turn segments prepared for surface examination of the organ of Corti. After gentamicin exposure, threshold shifts averaged a statistically reliable 33 dB in albinos and 19 dB for the pigmented animals. Anatomical studies revealed a significant 44% mean outer hair cell loss in albinos compared to a 21% loss in the pigmented inner ears. The results showed that albinos display greater ototoxicity from gentamicin than do pigmented guinea pigs. Aminoglycosides are known to exert toxicity through interaction with polyphosphoinositides found in high concentrations in the inner ear. Cochleae in both albino and pigmented animals appear to possess significant phospholipid concentrations and bind toxic levels of these drugs independent of inner ear pigment content. However, evidence showing that melanin can inhibit aminoglycoside activity in vitro suggests that, once these drugs bind to pigmented tissue, they may undergo inactivation in a manner unavailable to the nonpigmented albino cochlea. The present results are consistent with the possibility that cochlear melanin may inhibit gentamicin activity in vivo and decrease the severity of aminoglycoside ototoxicity in the pigmented inner ear.
Conlee
J W
JW
Veterans Administration Medical Center, Salt Lake City, Utah.
Gill
S S
SS
McCandless
P T
PT
Creel
D J
DJ
D000161:Acoustic Stimulation; D000417:Albinism / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects*; D001309:Auditory Threshold / Q000187:drug effects*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005839:Gentamicins / Q000633:toxicity*; D006168:Guinea Pigs / Q000378:metabolism*; D008543:Melanins / Q000502:physiology
D005839:Gentamicins; D008543:Melanins