Ototoxicity of sodium nitroprusside.
Nitric oxide (NO) not only has normal physiological roles like vasodilation and neurotransmission in the living organism, it could also have possible neurodestructive effects under certain pathological conditions. The present study aimed to determine whether direct exposure of guinea pig cochlea to a NO donor like sodium nitroprusside (SNP), or a nitric oxide synthase (NOS) inhibitor like N(G)-nitro-L-arginine methyl ester (L-NAME), would cause damage to the auditory hair cells. A piece of gelfoam was placed on the round window of the right ear of adult albino guinea pigs. It was then soaked with 0.1 ml of SNP (3.4 microM), 0.1 ml of L-NAME (9.3 microM or 18.5 microM) or 0.1 ml of injection water, the vehicle used to dissolve the above chemicals. Twelve animals receiving SNP were perfused 1 day, 2, 3 and 7 days later, with three animals being used for each survival period. Six animals receiving L-NAME were allowed to survive up to 7 days before perfusion. Eight animals receiving injection water or 0.45% saline were used as controls. With the scanning electron microscope, the inner and outer hair cells were counted over a 1 mm length of the basilar membrane in each turn of every cochlea. The results showed that, in animals treated with L-NAME at both concentrations stated, no significant loss of either inner or outer hair cells was noted in any part of the cochlea studied. However, as early as 1 day after SNP treatment, a striking loss of inner and outer hair cells was observed in the three lower turns of the cochlea. Damage to the outer hair cells was extended to the apical turn with increasing survival period, but no significant loss of inner hair cells was evident in the apical turn at any of the survival periods studied. To rule out the possibility that the effects were due to the presence of cyanide, a metabolite of SNP, hydroxycobalamin was introduced into the scala tympani of three animals through a cannula-osmotic pump device during SNP treatment. There was no significant difference in the results between the groups with and without hydroxycobalamin infusion 7 days after SNP treatment. The present study suggests that an excessive production of NO in the inner ear could lead to extensive loss of hair cells.
Ruan
R S
RS
Department of Otolaryngology, National University Hospital, Singapore. entrrs@leonis.nus.sg
Leong
S K
SK
Yeoh
K H
KH
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D006879:Hydroxocobalamin / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000633:toxicity*; D012405:Round Window, Ear / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006879:Hydroxocobalamin; D019331:NG-Nitroarginine Methyl Ester