The exact mechanism of salicylate ototoxicity, reversible sensorineural hearing loss and tinnitus, is still unknown and the studies on the transport mechanism into the cochlea seems to shed light on its generation mechanism.
In our previous studies, it has been concluded that the transport mechanism of furosemide andpenicillin G (organic anions) from the blood vessels into the perilymph is pronouncedly different between the scala tympani (ST) and the scala vestibuli (SV) of the guinea pig, i.e. active transport in ST and passive transport in SV. Aspirin (acetylsalicylic acid; ASA) and sodium salicylate (SA) are also organic anions. The goal of the present study is to examine the transport mechanism of ASA and SA in the cochlea of the guinea pigs and to determine whether the different transport system in two scalae is also present in case of ASA and SA.
In the present study, the sequential samples of ST and SV perilymph, cerebrospinal fluid (CSF) and serum were taken after intravenous administration of 100mg/kg of ASA or SA and the concentrations of ASA and SA were determined using high-performance liquid chromatography.
Because of the rapid hydrolysis of ASA to SA, with a elimination constant of 3.8×10
-3h
-1, there was no difference of the concentration or kinetic of SA in these body fluids between ASA and SA administration. In the serum, SA was relatively slowly eliminated with mean concentrations of 302 μg/ml and 155μg/ml at 5 minutes and 180 minutes after injection of SA (or ASA), respectively. The concentration of SA in CSF rapidly increased after administration of SA and reached the maximum value of 17.4μg/ml at 30 minutes. It was gradually declined thereafter (6.74μg/ml at 180 minutes). These kinetics of SA in the serum and CSF were analogous to those of furosemide and penicillin G.
In the ST perilymph, SA was slowly accumulated (2.92μg/ml at 5 minutes) and was not eliminated for following 3 hours after injection of ASA or SA (36.4μg/ml at 180 minutes). In contrast to the different kinetics of furosemide or penicillin G in ST from SV, the concentration of SA in the SV perilymph exhibited very similar time course to that in the ST perilymph.
The different transport mechanism of SA from furosemide or penicillin G in ST is suggested by the following view points;
1) No elimination of SA was found in ST at least for three hours, though there was a rapid elimination of furosemide after the early peak (at 15 minutes).
2) The kinetic of SA in ST was very similar to that in SV, while the concentrations of furosemide were very different between ST and SV perilymph.
3) The ST perilymph/serum gradient of SA was relatively low (1: 4.2, at 180minutes), compaired with furosemide (higher than 1: 65, at any time).
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